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Sahuquillo Torralba, P. Moles Poveda, G. Pérez Simó, J. Simarro Farinos, M. Llavador Ros, S. Palanca Suela, R. Botella Estrada" "autores" => array:8 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "de Unamuno Bustos" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Sahuquillo Torralba" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Moles Poveda" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Pérez Simó" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Simarro Farinos" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Llavador Ros" ] 6 => array:2 [ "nombre" => "S." "apellidos" => "Palanca Suela" ] 7 => array:2 [ "nombre" => "R." "apellidos" => "Botella Estrada" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0035"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219019300575" "doi" => "10.1016/j.adengl.2019.02.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219019300575?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731018304885?idApp=UINPBA000044" "url" => "/00017310/0000011000000003/v1_201904030618/S0001731018304885/v1_201904030618/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219019300538" "issn" => "15782190" "doi" => "10.1016/j.adengl.2019.02.014" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "2072" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2019;110:220-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Epidemiologic and Histopathologic Characterization of Cutaneous Metastases in Patients Who Visited 2 Hospitals in Santiago de Chile Between 2005 and 2017" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "220" "paginaFinal" => "226" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Caracterización epidemiológica e histopatológica de metástasis cutáneas en la población consultante de 2 hospitales de Santiago durante los años 2005 a 2017" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0055" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1085 "Ancho" => 1267 "Tamanyo" => 113857 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. Kaplan, C. Morales, F. Bobadilla, J. Fernández, L. Segovia, V. Vera, I. Sanhueza" "autores" => array:7 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Kaplan" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Morales" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Bobadilla" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Fernández" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Segovia" ] 5 => array:2 [ "nombre" => "V." "apellidos" => "Vera" ] 6 => array:2 [ "nombre" => "I." "apellidos" => "Sanhueza" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0055"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731018304381" "doi" => "10.1016/j.ad.2018.07.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731018304381?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219019300538?idApp=UINPBA000044" "url" => "/15782190/0000011000000003/v1_201904030645/S1578219019300538/v1_201904030645/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219019300629" "issn" => "15782190" "doi" => "10.1016/j.adengl.2018.12.009" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "2134" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2019;110:206-11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6 "formatos" => array:3 [ "EPUB" => 1 "HTML" => 3 "PDF" => 2 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Cutaneous Metastases From Breast Cancer: An 8-Year Review of Cases at a Tertiary Care Hospital" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "206" "paginaFinal" => "211" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Metástasis cutáneas de cáncer de mama: 8 años de revisión en un centro de tercera complejidad" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 927 "Ancho" => 900 "Tamanyo" => 59481 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Locoregional cutaneous metastasis, defined as a lesion on the same side as the primary tumor located below the clavicle and above the rib margin and limited medially by the sternum and laterally by the posterior axillary line. Cutaneous metastases were defined as lesions outside these limits.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Source: Lookingbill et al..<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D.P. Bastard, M.L. Bollea-Garlatti, A. Belatti, M.C. Puga, M.N. Hernández, L.D. Mazzuoccolo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "D.P." "apellidos" => "Bastard" ] 1 => array:2 [ "nombre" => "M.L." "apellidos" => "Bollea-Garlatti" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Belatti" ] 3 => array:2 [ "nombre" => "M.C." "apellidos" => "Puga" ] 4 => array:2 [ "nombre" => "M.N." "apellidos" => "Hernández" ] 5 => array:2 [ "nombre" => "L.D." "apellidos" => "Mazzuoccolo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731018305805" "doi" => "10.1016/j.ad.2018.12.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731018305805?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219019300629?idApp=UINPBA000044" "url" => "/15782190/0000011000000003/v1_201904030645/S1578219019300629/v1_201904030645/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Telomerase Expression in a Series of Melanocytic Neoplasms" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "212" "paginaFinal" => "219" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "De Unamuno Bustos B, Sahuquillo Torralba A, Moles Poveda P, Pérez Simó G, Simarro Farinos J, Llavador Ros M, Palanca Suela S, Botella Estrada R" "autores" => array:8 [ 0 => array:3 [ "nombre" => "De Unamuno" "apellidos" => "Bustos B" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Sahuquillo" "apellidos" => "Torralba A" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Moles" "apellidos" => "Poveda P" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Pérez" "apellidos" => "Simó G" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Simarro" "apellidos" => "Farinos J" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Llavador" "apellidos" => "Ros M" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 6 => array:4 [ "nombre" => "Palanca" "apellidos" => "Suela S" "email" => array:2 [ 0 => "palanca_sar@gva.es" 1 => "palanca_sar@gva.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 7 => array:3 [ "nombre" => "Botella" "apellidos" => "Estrada R" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Laboratorio de Biología Molecular, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio de la expresión de telomerasa en una serie de neoplasias melanocíticas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 638 "Ancho" => 850 "Tamanyo" => 239142 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mild telomerase expression in intradermal melanocytic nevus (x100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Telomerase is an enzyme made up of a catalytic subunit (telomerase reverse transcriptase or TERT) and a ribonucleic acid (TERC).<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> It is known to play a major role in telomere maintenance and cell senescence. Under normal conditions, it is only expressed in germline cells, fetal tissue, and stem cells. The somatic cells of other tissues lack telomerase activity, resulting in the progressive shortening of their telomeres after repeated cell division. Many studies have shown that telomerase activity is detected in more than 90% of malignant tumors,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> including different types of skin cancer.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> In melanocyte tumors in particular, several studies have identified increased telomerase activity in the neoplastic cells, from nevi to melanomas, with the highest telomerase activity detected in metastatic melanomas.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a> Furthermore, the role of <span class="elsevierStyleItalic">TERT</span> promoter mutations in the pathogenesis of melanoma has recently been demonstrated.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5,6</span></a> Several studies have identified recurring mutations in the <span class="elsevierStyleItalic">TERT</span> promoter region (c.1-146C>T, c.1-124C>T, c.1-124/-125CC>TT, c.1-138/-139CC>TT) in between 22% and 71% of sporadic melanomas associated with older patients, with melanomas in areas exposed to sunlight, of the nodular histologic subtype, a higher Breslow thickness, presence of ulceration, and high mitotic index.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7–9</span></a> Studies in tissue and cell lines have shown that these mutations produce increased expression of telomerase by creating new binding sites for transcription factors of the ETS family.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">9–12</span></a> The presence of these mutations has been shown to be an independent prognostic factor linked to reduced disease-free and overall survival.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8,13</span></a> Furthermore, this link to survival has been found to vary depending on the type of mutation identified, and is modified by the presence of rs2853669 polymorphism.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14,15</span></a> Recent studies have also shown the prognostic value of telomere length by identifying lower survival rates in patients with shorter telomeres.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16,17</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It therefore appears that telomerase expression plays a major role in melanoma carcinogenesis; however, few studies have analyzed telomerase expression at the protein level, and those studies include small series with few melanomas. Moreover, the study of telomerase expression may be of utility for stratifying patients based on prognosis. The objectives of this study are to analyze telomerase expression by means of immune staining in a series of melanomas (primary and metastatic) and melanocytic nevi, and to correlate expression levels with the clinical and pathologic characteristics and the course of the patients, and with mutations in the <span class="elsevierStyleItalic">TERT</span> promoter.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Selected Patients and Samples</span><p id="par0015" class="elsevierStylePara elsevierViewall">We performed a retrospective observational study in the Dermatology and Anatomical Pathology Department of Hospital Universitario y Politécnico La Fe, Valencia, Spain, in a sample of 85 patients diagnosed with melanoma and 22 patients diagnosed with melanocytic nevus (5 with intradermal nevus, 7 with compound nevus, and 10 with dysplastic nevus), who were seen at our department between January 1, 2014 and December 1, 2016. Samples with sufficient quantity of sample in the paraffin block were selected for immune staining. In the case of primary melanomas, the only samples included were those with an invasive component, classified in 4 main histologic subtypes (lentigo maligna melanoma, surface spreading melanoma, nodular melanoma, and acral lentiginous melanoma), and those for which a study of the <span class="elsevierStyleItalic">TERT</span> promoter was available. The primary tumor was studied in the 85 patients with melanoma and melanoma metastasis was also studied in 12 of these patients. The clinical and pathologic data of each of the patients with melanoma was collected. Breslow thickness was characterized using the classification of the American Joint Committee on Cancer (AJCC) (≤1.00, 1.01-2, 2.01-4, and > 4<span class="elsevierStyleHsp" style=""></span>mm)<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a>; the mitotic index was expressed as the number of cells undergoing mitosis per square millimeter and was characterized by the presence or absence of mitosis; histologic regression was defined as described in previous studies,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> and was characterized as absent or present, and growth rate was defined as described in previous studies.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> All patients provided written consent to take part in the study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Telomerase Expression With Immune Staining</span><p id="par0020" class="elsevierStylePara elsevierViewall">Immune staining was performed in 5-µm slices, using the hTERT monoclonal antibody (Rockland), as described previously.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> The same technique, with omission of the antibody, was used as a negative control. In the case of melanomas for which several blocks were available, those with the highest percentage of tumor cells were selected. Telomerase expression in all the samples included was performed by 2 independent observers (BU and RB). In the event of discrepancies in the observations of the 2 researchers, the observations of the researcher with most experience (RB) were used for the analysis. The extent of expression was quantified by establishing a score based on the percentage of positive cells (0, 0%; 1, < 10%; 2, 10%-50%; and 3, > 50%). The intensity of expression was scored from 0 to 3 (0, absent; 1, mild; 2, moderate; 3, intense). The expression pattern was classified as homogeneous or heterogeneous depending on the uniformity of expression in tumor cells.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical Analysis</span><p id="par0025" class="elsevierStylePara elsevierViewall">Descriptive analysis of the variables was performed using absolute and relative frequencies. Inferential analysis of the qualitative variables was performed using tests based on the χ<span class="elsevierStyleSup">2</span> distribution. Analysis of disease-free survival and overall survival was performed using the Kaplan-Meyer method. The degree of agreement between the independent observers was evaluated using the κ coefficient. Statistical analysis was performed using the SPSS statistical software package and statistical significance was established for values of p <0.05.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Telomerase Expression in Healthy Skin</span><p id="par0030" class="elsevierStylePara elsevierViewall">In the healthy skin surrounding the melanocytic lesions, telomerase expression was observed in the epidermis, hair follicles, sweat glands, and sebaceous glands, and in the endothelium of the dermal blood vessels. Expression was mild in the epidermis and follicles, moderate in the sweat glands, and intense in the sebaceous glands (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) <a class="elsevierStyleCrossRef" href="#sec0070">(Figs. S1- S3 of the additional material available in the online version)</a>. Expression in these appendages was used as a positive control in all the analyzed cases.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Telomerase Expression in Melanocytic Tumors</span><p id="par0035" class="elsevierStylePara elsevierViewall">The degree of agreement observed in the 3 parameters analyzed by the 2 researchers was good, with a κ index of 0.65 in intensity and 0.83 in extent, and 0.73 in telomerase expression pattern.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Telomerase was found to be expressed in all the melanocytic tumors analyzed. In the case of the primary melanomas, the expression pattern was homogeneous in all cell tumors in 59% (50/85) of cases (<a class="elsevierStyleCrossRef" href="#sec0070">Fig. S4 of the additional material</a>), whereas it was heterogeneous in 41% (35/85) of cases, with different expression intensity between tumor cells (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) (<a class="elsevierStyleCrossRef" href="#sec0070">Fig. S5 of the additional material</a>). In most of the cases analyzed (95%; 81/85), expression was observed in over 50% of tumor cells (Fig. S6 of the additional material), and expression in less than 10% of the tumorous infiltrate was only observed in 1 case (<a class="elsevierStyleCrossRef" href="#sec0070">Fig. S7 of the additional material</a>). In terms of intensity, expression was intense in 41% (35/85) of the samples (Fig. S8 of the additional material), moderate in 51% (43/85) (Fig. S9 of the additional material), and mild in only 8% (7/85) of the samples (<a class="elsevierStyleCrossRef" href="#sec0070">Fig. S10 of the additional material</a>). Melanomas with a precursor nevus lesion (5%; 4/85) revealed intense telomerase expression in the tumor cells of the melanoma but mild expression in the accompanying nevus cells (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A-3D).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In the metastatic melanomas, the expression pattern was homogeneous in 67% (8/12) and heterogeneous in 33% (4/12). Expression of hTERT was observed in over 50% of tumor cells in 100% of the samples, and was intense in 41% (5/12), moderate in 50% (6/12), and mild in 8.3% (1/12) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Telomerase expression revealed a homogeneous pattern in 100% of the melanocytic nevi, with an extent of over 50% in the tumor cells in 91% (20/22) of the samples. Expression intensity was mild in 64% (14/22), moderate in 32% (7/22), and intense in 4% (1/22) of the samples. (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In terms of differences in expression based on the clinical and pathologic characteristics of the primary melanomas, the heterogeneous expression pattern was associated with fast-growing melanomas (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.028) with a Breslow thickness of more than 4<span class="elsevierStyleHsp" style=""></span>mm (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,004), with mitosis (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.032), and with mutations in the <span class="elsevierStyleItalic">TERT</span> promoter (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,002) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The expression pattern showed no significant differences between the type of mutation in the <span class="elsevierStyleItalic">TERT</span> promoter (c.1-146C>T, c.1-124C>T, and c.1-124/-125CC>TT). No statistically significant differences were observed in intensity or extent of expression (Table S1 of the additional material). Expression intensity was higher in melanomas of the lentigo maligna melanoma subtype and lower in acral lentiginous melanomas, although this difference was not statistically significant (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.523). Analysis of survival revealed no statistically significant differences based on telomerase expression.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The comparative analysis of nevus with primary and metastatic melanoma revealed that telomerase expression in the nevi was less intense than in the primary and metastatic melanomas (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001) and that, unlike the melanomas, the nevi revealed a characteristic pattern of homogeneous expression in all the tumor cells (p < 0.001) (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). No statistically significant differences were observed between primary and metastatic melanomas. Moreover, in the case of the nevi, intensity was lowest in the intradermal nevi, followed by the compound and dysplastic nevi, although the differences were not statistically significant (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.054).</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The results of this study show that telomerase expression occurs in all the melanocytic tumors analyzed, and that a gradually increasing trend from nevus to melanoma exists, which may be implicated in the tumor progression in this type of cancer.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In the primary melanomas in our series, we showed that the heterogeneous expression pattern is associated with more aggressive melanomas (faster-growing melanomas with a tumor thickness of more than 4<span class="elsevierStyleHsp" style=""></span>mm, with mitosis, and with mutations in the <span class="elsevierStyleItalic">TERT</span> promoter); this has not been previously reported. These results contrast with those recently reported by Hugdahl et al,<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> who describe homogeneous expression in most of their cases. Our findings, however, may support those reported by Kohli et al,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> who report heterogeneous expression of non-nuclear telomerase in melanomas but not in benign lesions. This heterogeneous expression pattern may be the result of intratumoral heterogeneity in melanoma, which has been linked to different tumor subpopulations, and is linked to resistance to systemic treatments.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">24,25</span></a> Furthermore, we cannot rule out the possibility that the heterogeneity observed in our study may be due to a defect in the staining procedure, although this is unlikely, as this pattern was not observed in any of the benign melanocytic lesions.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Unlike other studies, in our series, the intensity and extent of telomerase expression were independent of the clinical and pathologic characteristics. Hugdahl et al<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> reported a statistically significant link between telomerase expression (44% of primary melanomas in that series) and tumor thickness, and Zygouris et al<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> described a link with Breslow thickness and ulceration. Our findings contrast with several studies that have analyzed telomerase activity, such as the study by Ramírez et al, which found greater telomerase activity in melanomas with greater tumor thickness, a higher Clark score, and mitosis<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a>; the results of Miracco et al,<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> in which telomerase activity was also associated with Breslow thickness and the Clark score; and the study by Carvalho et al,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a> which found greater telomerase activity in ulcerated melanomas, with a greater Breslow thickness, mitosis, vascular invasion, and satellitosis. In our series, melanomas of lentigo maligna melanoma showed greater expression intensity, although this did not reach statistical significance. This last finding does not support the findings of the series by Pópulo et al,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> in which telomerase expression was only associated with the surface spreading histologic subtype.</p><p id="par0080" class="elsevierStylePara elsevierViewall">With respect to the mutations in the <span class="elsevierStyleItalic">TERT</span> promoter, in line with reporting by other authors,<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8,9</span></a> in a previous publication,<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> we reported a prevalence of 33% and an association with ulcerated melanomas with greater tumor thickness, with mitosis, and of the nodular histologic subtype. As in other studies, in this series, we found no differences using immune staining in telomerase expression between mutated and nonmutated melanomas.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8,22,23</span></a> This finding contrasts with several prior publications, which found greater telomerase expression in melanomas with mutations in the promoter.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">9–12</span></a> This discrepancy may be due to the fact that those studies analyzed telomerase expression at the messenger RNA level and not at the protein level, and other molecular mechanisms may therefore exist that regulate telomerase expression. Indeed, several studies have focused on epigenetic regulation of telomerase expression. It has been reported that post-transcriptional regulation of the <span class="elsevierStyleItalic">TERT</span> through microRNA expression may suppress telomerase expression<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">31,32</span></a> and that hypermethylation in the DNA of the <span class="elsevierStyleItalic">TERT</span> gene may increase telomerase expression.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> It may therefore be useful to measure the length of the telomeres and/or telomerase activity and correlate it to the presence of the mutation in order to determine whether only mutated genes show increased activity or whether wild-type genes also show greater telomerase activity through these other molecular mechanisms.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Furthermore, we have identified variable levels of telomerase expression in a series of 22 melanocytic nevi with mild expression in most of the samples, and a tendency for expression to increase from intradermal nevi to dysplastic nevi. It should also be noted that, in all the melanomas with a nevus precursor, telomerase expression in the accompanying nevus was much less intense than in the tumor cells of the melanoma. These results suggest a potential role of telomerase in tumor progression in melanocytic cancers. Several authors have analyzed telomerase activity in different types of melanocytic tumor and have found that telomerase expression increases progressively from common nevi to dysplastic nevi and melanomas.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4,34</span></a> These differences in telomerase expression between nevus and melanoma, however, have been found not to be of use in the differential diagnosis, as expression may be variable in both types of tumor.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In this study, telomerase expression was analyzed using immune staining, unlike most previously published studies, which analyzed telomerase activity using the telomere repeat amplification protocol (TRAP).<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4,23–25</span></a> Immune staining has the advantage of being a simple and cheap method that is performed using paraffinized samples and makes it possible to visualize the intensity and extent of expression, not only in the cells of interest but also in adjacent healthy skin. Indeed, in line with what has already been described,<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a> we have identified variable levels of telomerase expression, not only in the tumor cells but also in the epidermis, hair follicles, glands, dermal blood vessels, and even in the accompanying inflammatory infiltrate.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion, the results of this study show that telomerase expression occurs in all the analyzed melanocytic tumors, with greater expression in the melanomas than in the nevi. In the case of the primary melanomas, heterogeneous expression is linked to a more aggressive phenotype; however, expression intensity is independent of the clinical and pathologic characteristics of the tumors. It has also been shown that no differences exist in telomerase expression based on the mutational state of the <span class="elsevierStyleItalic">TERT</span> gene and other molecular mechanisms must therefore exist that regulate expression of the <span class="elsevierStyleItalic">TERT</span> gene in the melanomas.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">This study was carried out with grants awarded by Fundación Piel Sana (EUROMELANOMA 2016 grant from the AEDV Foundation), Carlos III Institute of Health (ISCII) (PI16/01559), IISLaFe (2014/0370), and the Department of Education, Research, Culture and Sport of the autonomous government of Valencia (GV/2016/064).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of Interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1174034" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1097954" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1174035" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1097955" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Selected Patients and Samples" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Telomerase Expression With Immune Staining" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Telomerase Expression in Healthy Skin" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Telomerase Expression in Melanocytic Tumors" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-04-13" "fechaAceptado" => "2018-10-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1097954" "palabras" => array:5 [ 0 => "Telomerase" 1 => "Telomerase reverse transcriptase (TERT)" 2 => "Melanoma" 3 => "Nevus" 4 => "Immunohistochemistry" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1097955" "palabras" => array:5 [ 0 => "Telomerasa" 1 => "<span class="elsevierStyleItalic">Telomerase reverse transcriptase</span> (TERT)" 2 => "Melanoma" 3 => "Nevus" 4 => "Inmunohistoquimia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (<span class="elsevierStyleItalic">P<span class="elsevierStyleHsp" style=""></span></span>=<span class="elsevierStyleHsp" style=""></span>.028), a Breslow thickness of more than 4<span class="elsevierStyleHsp" style=""></span>mm (<span class="elsevierStyleItalic">P<span class="elsevierStyleHsp" style=""></span></span>=<span class="elsevierStyleHsp" style=""></span>.004), mitosis (<span class="elsevierStyleItalic">P<span class="elsevierStyleHsp" style=""></span></span>=<span class="elsevierStyleHsp" style=""></span>.032), and mutations in the <span class="elsevierStyleItalic">TERT</span> gene (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (<span class="elsevierStyleItalic">P<span class="elsevierStyleHsp" style=""></span></span>=<span class="elsevierStyleHsp" style=""></span>.054).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La telomerasa es una enzima implicada en el mantenimiento de los telómeros y la senescencia celular. Numerosos estudios han demostrado que en más del 90% de las neoplasias malignas se detecta actividad telomerásica. El objetivo del presente estudio es analizar la expresión de telomerasa por inmunohistoquímica en una serie de neoplasias melanocíticas.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo realizado en una serie de 85 melanomas primarios, 12 metastásicos y 22 nevus melanocíticos. La expresión de telomerasa se analizó empleando el anticuerpo monoclonal hTERT (Rockland). El análisis de los datos se realizó con el programa SPSS.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En todas las neoplasias melanocíticas analizadas se demostró expresión de telomerasa. En el caso de los melanomas predominó el patrón de expresión heterogéneo, y la expresión moderada o intensa. En los nevus resultó más frecuente una expresión homogénea con intensidad leve. El patrón de expresión heterogéneo se asoció a los melanomas de rápido crecimiento (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,028), con Breslow > 4<span class="elsevierStyleHsp" style=""></span>mm (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,004), con mitosis (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,032), y con mutaciones en el gen TERT (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,002). En el caso de los nevus, la intensidad fue menor en los nevus intradérmicos, seguidos de los compuestos y de los diplásicos (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,054).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La expresión de telomerasa está presente en la totalidad de las neoplasias melanocíticas, con mayor expresión en los melanomas que en los nevus. En el caso de los melanomas, la expresión de forma heterogénea se asocia a un fenotipo de mayor agresividad.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Bustos BdU, Torralba AS, Poveda PM, Simó GP, Farinos JS, Ros ML, et al. Estudio de la expresión de telomerasa en una serie de neoplasias melanocíticas. Actas Dermosifiliogr. 2019;110:212–219.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0120" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0070" ] ] ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 637 "Ancho" => 850 "Tamanyo" => 237221 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Intense telomerase expression in sebaceous glands (x100).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 638 "Ancho" => 850 "Tamanyo" => 267805 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Telomerase expression with a heterogeneous pattern in primary melanoma (x100).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 994 "Ancho" => 1300 "Tamanyo" => 736109 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A, Melanoma associated with intradermal nevus (hematoxylin–eosin, x40). B, Detail of intradermal nevus associated with the melanoma (hematoxylin–eosin, x100). C, Intense telomerase expression in melanoma tumor cells and mild expression in nevus cells (x40). D, Detail of mild telomerase expression in the nevus cells (x100).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 638 "Ancho" => 850 "Tamanyo" => 296591 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Intense telomerase expression in metastatic melanoma (x100).</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 638 "Ancho" => 850 "Tamanyo" => 239142 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mild telomerase expression in intradermal melanocytic nevus (x100).</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 891 "Ancho" => 2917 "Tamanyo" => 135694 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">A, Telomerase expression pattern in melanoma and nevus with predominantly homogeneous expression in melanocytic nevi. B, Progressive reduction in intensity of telomerase expression from metastatic melanomas to nevi.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Het indicates heterogeneous; Hom, homogeneous; WT, wild type.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Total (n = 85) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Expression pattern</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Hom \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Het \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">p \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Age</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>< 40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (5.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (60.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.678 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>40-65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (52.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (60.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>> 65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (41.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (60.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 (54.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 (63.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (37.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.526 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 (45.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (53.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Location</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Head and neck \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (10.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (22.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (77.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.025 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Torso \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (52.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 (71.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (28.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Upper limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (16.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lower limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (16.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Histologic subtype</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lentigo maligna melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.017 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Surface spreading melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 (75.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (67.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (32.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nodular melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acral lentiginous melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Breslow thickness</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>< 1 mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 (47.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 (72.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (27.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> 1-2 mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 (34.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (55.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (44.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> 2-4 mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> > 4 mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (11.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (10.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (90.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Ulceration</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69 (81.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (62.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (37.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.141 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 (18.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (43.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (56.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Mitosis</span>/mm<span class="elsevierStyleSup">2</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> < 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (50.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (69.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (30.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.032 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> ≥ 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 (49.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (47.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (52.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Regression</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (50.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (53.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 (46.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.215 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 (49.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Tumor stage</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Local \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73 (85.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (59.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 (40.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.580 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Local-regional/distant disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (14.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (58.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (41.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Growth rate</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Slow growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 (82.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.028 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Rapid growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (17.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Clinical course (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Stable disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69 (81.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 (57.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (42.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.242 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Local-regional/distant relapse \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (13.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (42.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (57.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (6.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Mutations in TERT promoter</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> WT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61 (71.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 (66.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (33.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span> Mutated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (28.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (27.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (72.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2003833.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Clinical and Pathologic Characteristics of Patients With Melanoma and Distribution of Characteristics Based on the Telomerase Expression Pattern.</p>" ] ] 7 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 89909 ] ] 8 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.pdf" "ficheroTamanyo" => 26664118 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0175" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TERT promoter mutations in telomere biology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. 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año/Mes | Html | Total | |
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2024 Noviembre | 8 | 10 | 18 |
2024 Octubre | 72 | 38 | 110 |
2024 Septiembre | 73 | 19 | 92 |
2024 Agosto | 79 | 55 | 134 |
2024 Julio | 67 | 31 | 98 |
2024 Junio | 76 | 27 | 103 |
2024 Mayo | 66 | 44 | 110 |
2024 Abril | 77 | 28 | 105 |
2024 Marzo | 56 | 36 | 92 |
2024 Febrero | 57 | 44 | 101 |
2024 Enero | 56 | 49 | 105 |
2023 Diciembre | 58 | 19 | 77 |
2023 Noviembre | 57 | 30 | 87 |
2023 Octubre | 74 | 38 | 112 |
2023 Septiembre | 52 | 28 | 80 |
2023 Agosto | 46 | 23 | 69 |
2023 Julio | 47 | 40 | 87 |
2023 Junio | 37 | 23 | 60 |
2023 Mayo | 55 | 22 | 77 |
2023 Abril | 35 | 20 | 55 |
2023 Marzo | 50 | 20 | 70 |
2023 Febrero | 49 | 19 | 68 |
2023 Enero | 32 | 33 | 65 |
2022 Diciembre | 52 | 32 | 84 |
2022 Noviembre | 39 | 22 | 61 |
2022 Octubre | 25 | 25 | 50 |
2022 Septiembre | 20 | 26 | 46 |
2022 Agosto | 20 | 29 | 49 |
2022 Julio | 25 | 34 | 59 |
2022 Junio | 22 | 24 | 46 |
2022 Mayo | 69 | 56 | 125 |
2022 Abril | 127 | 31 | 158 |
2022 Marzo | 120 | 47 | 167 |
2022 Febrero | 131 | 23 | 154 |
2022 Enero | 114 | 39 | 153 |
2021 Diciembre | 61 | 38 | 99 |
2021 Noviembre | 102 | 45 | 147 |
2021 Octubre | 42 | 56 | 98 |
2021 Septiembre | 28 | 40 | 68 |
2021 Agosto | 31 | 21 | 52 |
2021 Julio | 22 | 25 | 47 |
2021 Junio | 21 | 24 | 45 |
2021 Mayo | 35 | 37 | 72 |
2021 Abril | 41 | 32 | 73 |
2021 Marzo | 39 | 33 | 72 |
2021 Febrero | 54 | 16 | 70 |
2021 Enero | 30 | 23 | 53 |
2020 Diciembre | 26 | 16 | 42 |
2020 Noviembre | 22 | 19 | 41 |
2020 Octubre | 29 | 9 | 38 |
2020 Septiembre | 35 | 13 | 48 |
2020 Agosto | 23 | 20 | 43 |
2020 Julio | 26 | 15 | 41 |
2020 Junio | 21 | 20 | 41 |
2020 Mayo | 16 | 12 | 28 |
2020 Abril | 26 | 18 | 44 |
2020 Marzo | 12 | 6 | 18 |
2020 Febrero | 3 | 0 | 3 |
2019 Mayo | 1 | 0 | 1 |
2019 Abril | 1 | 1 | 2 |