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RF - Polyomavirus Oncoprotein Antibodies in Merkel Cell Carcinoma: A Marker of Disease Progression and Prognosis
FR - Anticuerpos contra la oncoproteína del poliomavirus en el carcinoma de células de Merkel: marcador pronóstico y evolutivo
A. Tomás-Velázquez
, N. Rodríguez-Garijo, P. Redondo
Corresponding author
Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
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B, Calculated tumor area (CTA). To calculate CTA, construct a box in the Breslow thickness measurement area that includes the entire invasive melanoma and estimate the percentage of the area occupied by invasive cells. Measure the height and width of the box (mm) using the microscope objective lens diameter. The formula for calculating CTA is height × width × proportion. For example, if the objective measures 5 mm, the box (as shown in the Fig.) measures 3 lenses high and 4 lenses wide, and the area occupied by tumor cells is 20%, the CTA would be 15 × 20 × 20/100 = 60 mm<span class="elsevierStyleSup">2</span>. C, Breslow density. To calculate Breslow density, at the ×10 magnification, construct a window in the Breslow measurement area, the bottom of which is limited by the deepest melanoma cell and the top of which is limited by the basement membrane. The width is determined by the width of the magnification field. Horizontally move the window to the area of the dermis with the highest density of melanoma, whilst keeping the deepest melanoma cell within the window. The proportion of the dermis occupied by melanoma cells is expressed with a precision of 5% (for scores < 5% or > 95%, use a precision of 1%).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "X. Bosch-Amate, P. Vargas-Mora, D. Morgado-Carrasco" "autores" => array:3 [ 0 => array:2 [ "nombre" => "X." "apellidos" => "Bosch-Amate" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Vargas-Mora" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S000173102100199X" "doi" => "10.1016/j.ad.2019.10.018" "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/S000173102100199X?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021002900?idApp=UINPBA000044" "url" => "/15782190/0000011200000010/v1_202111080506/S1578219021002900/v1_202111080506/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Resident’s Forum</span>" "titulo" => "RF - Polyomavirus Oncoprotein Antibodies in Merkel Cell Carcinoma: A Marker of Disease Progression and Prognosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "924" "paginaFinal" => "925" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Tomás-Velázquez, N. Rodríguez-Garijo, P. Redondo" "autores" => array:3 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Tomás-Velázquez" "email" => array:1 [ 0 => "atomasv@unav.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Rodríguez-Garijo" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Redondo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "FR - Anticuerpos contra la oncoproteína del poliomavirus en el carcinoma de células de Merkel: marcador pronóstico y evolutivo" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma characterized by high mortality and a tendency to local recurrence and metastasis. Classically, MCC patients have been treated with combinations of surgery, radiotherapy, and intensive chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The Food and Drug Administration of the United States approved immunotherapy with the anti-programmed death-ligand 1 (PD-L1) agent avelumab and the anti-programmed cell death protein 1 (PD-1) agent pembrolizumab for the treatment of patients with MCC. While much MCC research has focused on immunotherapy, there have been important advances in patient follow-up, specifically focusing on Merkel cell polyomavirus antibodies.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In October 2010, Paulson and coworkers published 2 important findings in Cancer Research based on their comparison of 205 MCC cases and 530 controls.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> First, they reported that MCC patients presented sustained increases in serum levels of antibodies against Merkel cell polyomavirus capsid proteins. However, the utility of these antibodies was limited by the fact that they were also detected in more than half of the healthy controls, indicating a previous Merkel cell polyomavirus infection. Furthermore, the authors found that antibodies against tumor-associated antigens (polyomavirus oncoproteins) were more specifically associated with MCC: these antibodies were detected in 0.9% of controls (and were of low titer) compared with 40.5% of MCC patients. They also observed differences in the levels of these antibodies depending on the disease course: titers were lower in patients without recurrence and higher in those in which the disease progressed.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">More recently, the same group published the results of a prospective validation study conducted in a cohort of 219 patients recently diagnosed with MCC and followed up for a median of 1.9 years. Seropositive patients (i.e. those with positive antibodies against polyomavirus oncoproteins) had less aggressive tumors, regardless of age, sex, staging, and immune status. In seropositive patients with a satisfactory response to treatment and without recurrence, titers of these antibodies decreased to below detectable levels within a median of 8.4 months. Furthermore, increases and decreases in antibody titers during follow-up had positive and negative predictive values for recurrence of 66% and 97%, respectively.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Therefore, the determination of antibody titers against polyomavirus oncoproteins at baseline (before treatment initiation) and during evolution (in the case of seropositive patients) is useful for both prognosis and follow-up.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> In fact, this serological test has been included in the 2018 National Comprehensive Cancer Network’s MCC guidelines, which state the following: “quantification of Merkel cell polyomavirus oncoprotein antibodies may be considered as a part of initial workup; seronegative patients may have a higher risk of recurrence; in seropositive patients, a rising titer may be an early indicator of recurrence”.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Treatment and follow-up of MCC patients requires a multidisciplinary team, in which the dermatologist plays a fundamental role. Dermatological oncology reference centers could perhaps consider implementing serology for polyomavirus oncoprotein owing to its utility in the follow-up of these patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1437808" "palabras" => array:7 [ 0 => "Merkel cell carcinoma" 1 => "Polyomavirus" 2 => "Serology" 3 => "Antibodies" 4 => "Recurrence" 5 => "Prognosis" 6 => "Marker" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Tomás-Velázquez A, Rodríguez-Garijo N, Redondo P. FR - Anticuerpos contra la oncoproteína del poliomavirus en el carcinoma de células de Merkel: marcador pronóstico y evolutivo. Actas Dermosifiliogr. 2021;112:924–925.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and epidemiological characteristics of Merkel cell carcinoma in a series of 38 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Dañino-García" 1 => "J.J. Domínguez-Cruz" 2 => "C. Pérez-Ruiz" 3 => "J. Conejo-Mir" 4 => "J.J. 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