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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">First we wish to congratulate the authors of the case report <span class="elsevierStyleItalic">Extraocular Sebaceous Carcinoma</span>&#44; published in volume 103 of <span class="elsevierStyleItalic">Actas Dermo-Sifiliogr&#225;ficas</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We believe that much can be learned from the 2 cases described&#44; which furthermore highlight the role of the dermatologist as the first specialist in a position to detect serious diseases&#46; We have had a similar experience&#44; and wish to describe the molecular and genetic tests that are available for these types of cases&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was 47 years of age and was diagnosed with extraocular sebaceous carcinoma&#46; He was referred for follow-up&#44; during which we detected several sebaceous adenomas and hyperplasias&#44; which were excised because malignancy could not be clinically ruled out&#46; Given that some of these lesions displayed varying degrees of dysplasia&#44; samples were analyzed for microsatellite instability&#44; which was positive&#44; in an initial immunohistochemical screening&#46; Based on these data and faced with a suspected case of Muir-Torre syndrome &#40;MTS&#41;&#44; a detailed analysis of family cancer history was conducted&#46; This revealed the presence of several first- and second-degree relatives who had died from colon and urothelial cancer&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">MTS is a highly penetrant autosomal dominant disease&#44; which is either inherited or arises spontaneously&#46; It affects patients who are heterozygous for the causative mutation and shares a common genetic basis with hereditary nonpolyposis colon cancer &#40;<span class="elsevierStyleItalic">hMSH2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> MTS is characterized by the presence of multiple sebaceous gland tumors&#44; including sebaceous hyperplasia&#44; sebaceous adenoma&#44; sebaceous epithelioma&#44; sebaceous carcinoma&#44; keratoacanthoma&#44; and various visceral tumors&#44; including colorectal&#44; gastric&#44; esophageal&#44; breast&#44; and genitourinary tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">MTS is caused by mutations that affect DNA mismatch repair &#40;MMR&#41; proteins&#46; The MMR proteins most closely associated with MTS are MSH2&#44; MLH1&#44; and MHS6&#44; although PMS22 and MLH3 have also been recently implicated&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> At our hospital&#44; we perform immunohistochemistry for MSH2&#44; MSH6&#44; MLH1&#44; and PMS2 proteins in all suspected cases of MTS&#46; If these proteins are not expressed&#44; as occurred with our patient&#44; the next step is an analysis of DNA microsatellite instability&#46; In our case a microsatellite instability &#40;MSI&#41; analysis was performed by polymerase chain reaction &#40;PCR&#41; amplification of a panel of 5 markers &#40;BAT-25&#44; BAT-26&#44; NR-21&#44; NR-24&#44; and MONO-27&#41; and 2 control markers &#40;Penta C and Penta D&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">PCR was subsequently performed with specific fluorescent primers using MSI Analysis System Version 1&#46;2 &#40;Promega&#41;&#44; and fragment analysis was conducted using an ABI Prism 3730 sequencer and the corresponding software&#46; These tests revealed high-level microsatellite instability&#46; Specifically&#44; instability of the following markers was observed&#58; NR-21&#44; BAT-25&#44; BAT-26&#44; and MONO-27&#46; The next stage consisted of automated extraction of DNA from the tumor samples and sequencing of exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene&#44; followed by electrophoresis and sequencing analysis &#40;ABI3730&#59; SeqScape v 2&#46;5&#41;&#46; Direct molecular analysis of mutation c&#46;1544&#95;1548delCAGTG of exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene was positive&#46; The sensitivity of this technique is 99&#46;9&#37;&#46; Analysis of a sample of the patient&#39;s peripheral blood using the same approach identified the same alteration&#46; Subsequent analyses of the peripheral blood of the patient&#39;s immediate relatives &#40;3 siblings and 2 children&#41; were positive for the 1544&#95;1548 mutation of CAGTG in exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene in 1 of the siblings and 1 of the children&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All mutation carriers were included in a screening program for individuals with a high risk of colon adenocarcinoma and urothelial cancer&#44; and female carriers underwent exhaustive gynecological examinations&#46; During the following 2 years our patient presented multiple colonic tubular adenomas with high-grade dysplasia&#44; and finally underwent a prophylactic subtotal colectomy due to the impossibility of controlling flat adenomas&#46; We detected 2 new sebaceous carcinomas of less than 3<span class="elsevierStyleHsp" style=""></span>mm in diameter&#44; one on the face and another on the forearm&#46; There was no clinical evidence of malignancy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sebaceous carcinoma can appear benign and unremarkable&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and can sometimes resemble other lesions&#46; This neoplasm is an adnexal malignant tumor derived from the epithelium of the ocular &#40;meibomian&#41; or extraocular sebaceous glands&#46; It is locally very aggressive and has a strong tendency toward vascular and perineural invasion and local recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Multiple studies indicate that all patients in whom sebaceous neoplasia is detected should undergo testing to rule out internal visceral tumors&#44; and where possible avail of the appropriate molecular and genetic tests&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is particularly important to identify these individuals&#44; as peripheral blood tests can also detect instability markers&#44; which are important to identify relatives carrying the mutation early in life and prior to the onset of symptoms&#46; The risk of transmitting the mutation is 50&#37; for each child and prenatal diagnosis is possible in these families&#46;</p></span>"
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Letter to the editor
Microsatellite and Genetic Instability in Patients With Muir-Torre Syndrome
Estudio de inestabilidad de microsatélites y genético de los pacientes con síndrome de Muir-Torre
A.I. Lorente-Lavirgena,
Autor para correspondencia
ariselae84@gmail.com

Corresponding Author.
, M. Morillo-Andújara, T. Zulueta-Doradob, J. Conejo-Mira
a Servicio de Dermatología y Venereología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
b Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">First we wish to congratulate the authors of the case report <span class="elsevierStyleItalic">Extraocular Sebaceous Carcinoma</span>&#44; published in volume 103 of <span class="elsevierStyleItalic">Actas Dermo-Sifiliogr&#225;ficas</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We believe that much can be learned from the 2 cases described&#44; which furthermore highlight the role of the dermatologist as the first specialist in a position to detect serious diseases&#46; We have had a similar experience&#44; and wish to describe the molecular and genetic tests that are available for these types of cases&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was 47 years of age and was diagnosed with extraocular sebaceous carcinoma&#46; He was referred for follow-up&#44; during which we detected several sebaceous adenomas and hyperplasias&#44; which were excised because malignancy could not be clinically ruled out&#46; Given that some of these lesions displayed varying degrees of dysplasia&#44; samples were analyzed for microsatellite instability&#44; which was positive&#44; in an initial immunohistochemical screening&#46; Based on these data and faced with a suspected case of Muir-Torre syndrome &#40;MTS&#41;&#44; a detailed analysis of family cancer history was conducted&#46; This revealed the presence of several first- and second-degree relatives who had died from colon and urothelial cancer&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">MTS is a highly penetrant autosomal dominant disease&#44; which is either inherited or arises spontaneously&#46; It affects patients who are heterozygous for the causative mutation and shares a common genetic basis with hereditary nonpolyposis colon cancer &#40;<span class="elsevierStyleItalic">hMSH2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> MTS is characterized by the presence of multiple sebaceous gland tumors&#44; including sebaceous hyperplasia&#44; sebaceous adenoma&#44; sebaceous epithelioma&#44; sebaceous carcinoma&#44; keratoacanthoma&#44; and various visceral tumors&#44; including colorectal&#44; gastric&#44; esophageal&#44; breast&#44; and genitourinary tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">MTS is caused by mutations that affect DNA mismatch repair &#40;MMR&#41; proteins&#46; The MMR proteins most closely associated with MTS are MSH2&#44; MLH1&#44; and MHS6&#44; although PMS22 and MLH3 have also been recently implicated&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> At our hospital&#44; we perform immunohistochemistry for MSH2&#44; MSH6&#44; MLH1&#44; and PMS2 proteins in all suspected cases of MTS&#46; If these proteins are not expressed&#44; as occurred with our patient&#44; the next step is an analysis of DNA microsatellite instability&#46; In our case a microsatellite instability &#40;MSI&#41; analysis was performed by polymerase chain reaction &#40;PCR&#41; amplification of a panel of 5 markers &#40;BAT-25&#44; BAT-26&#44; NR-21&#44; NR-24&#44; and MONO-27&#41; and 2 control markers &#40;Penta C and Penta D&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">PCR was subsequently performed with specific fluorescent primers using MSI Analysis System Version 1&#46;2 &#40;Promega&#41;&#44; and fragment analysis was conducted using an ABI Prism 3730 sequencer and the corresponding software&#46; These tests revealed high-level microsatellite instability&#46; Specifically&#44; instability of the following markers was observed&#58; NR-21&#44; BAT-25&#44; BAT-26&#44; and MONO-27&#46; The next stage consisted of automated extraction of DNA from the tumor samples and sequencing of exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene&#44; followed by electrophoresis and sequencing analysis &#40;ABI3730&#59; SeqScape v 2&#46;5&#41;&#46; Direct molecular analysis of mutation c&#46;1544&#95;1548delCAGTG of exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene was positive&#46; The sensitivity of this technique is 99&#46;9&#37;&#46; Analysis of a sample of the patient&#39;s peripheral blood using the same approach identified the same alteration&#46; Subsequent analyses of the peripheral blood of the patient&#39;s immediate relatives &#40;3 siblings and 2 children&#41; were positive for the 1544&#95;1548 mutation of CAGTG in exon 10 of the <span class="elsevierStyleItalic">MSH2</span> gene in 1 of the siblings and 1 of the children&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All mutation carriers were included in a screening program for individuals with a high risk of colon adenocarcinoma and urothelial cancer&#44; and female carriers underwent exhaustive gynecological examinations&#46; During the following 2 years our patient presented multiple colonic tubular adenomas with high-grade dysplasia&#44; and finally underwent a prophylactic subtotal colectomy due to the impossibility of controlling flat adenomas&#46; We detected 2 new sebaceous carcinomas of less than 3<span class="elsevierStyleHsp" style=""></span>mm in diameter&#44; one on the face and another on the forearm&#46; There was no clinical evidence of malignancy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sebaceous carcinoma can appear benign and unremarkable&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and can sometimes resemble other lesions&#46; This neoplasm is an adnexal malignant tumor derived from the epithelium of the ocular &#40;meibomian&#41; or extraocular sebaceous glands&#46; It is locally very aggressive and has a strong tendency toward vascular and perineural invasion and local recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Multiple studies indicate that all patients in whom sebaceous neoplasia is detected should undergo testing to rule out internal visceral tumors&#44; and where possible avail of the appropriate molecular and genetic tests&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is particularly important to identify these individuals&#44; as peripheral blood tests can also detect instability markers&#44; which are important to identify relatives carrying the mutation early in life and prior to the onset of symptoms&#46; The risk of transmitting the mutation is 50&#37; for each child and prenatal diagnosis is possible in these families&#46;</p></span>"
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2016 Diciembre 30 2 32
2016 Noviembre 33 5 38
2016 Octubre 33 22 55
2016 Septiembre 47 10 57
2016 Agosto 39 3 42
2016 Julio 40 5 45
2016 Junio 9 6 15
2016 Mayo 15 5 20
2016 Abril 3 1 4
2016 Marzo 3 1 4
2016 Febrero 5 2 7
2016 Enero 5 1 6
2015 Diciembre 16 6 22
2015 Noviembre 8 6 14
2015 Octubre 5 4 9
2015 Septiembre 3 1 4
2015 Agosto 5 5 10
2015 Julio 19 5 24
2015 Junio 16 5 21
2015 Mayo 27 3 30
2015 Abril 19 10 29
2015 Marzo 24 4 28
2015 Febrero 22 10 32
2015 Enero 7 7 14
2014 Diciembre 24 5 29
2014 Noviembre 18 8 26
2014 Octubre 25 11 36
2014 Septiembre 49 9 58
2014 Agosto 35 17 52
2014 Julio 29 16 45
2014 Junio 35 19 54
2014 Mayo 54 22 76
2014 Abril 46 6 52
2014 Marzo 44 11 55
2014 Febrero 17 13 30
2014 Enero 20 25 45
2013 Diciembre 79 33 112
2013 Noviembre 129 19 148
2013 Octubre 97 11 108
2013 Septiembre 27 9 36
2013 Agosto 0 1 1
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Idiomas
Actas Dermo-Sifiliográficas
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?