Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomaviru...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Modern pathology 2015-08, Vol.28 (8), p.1023-1032
Hauptverfasser: Pulitzer, Melissa P, Brannon, A Rose, Berger, Michael F, Louis, Peter, Scott, Sasinya N, Jungbluth, Achim A, Coit, Daniel G, Brownell, Isaac, Busam, Klaus J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1032
container_issue 8
container_start_page 1023
container_title Modern pathology
container_volume 28
creator Pulitzer, Melissa P
Brannon, A Rose
Berger, Michael F
Louis, Peter
Scott, Sasinya N
Jungbluth, Achim A
Coit, Daniel G
Brownell, Isaac
Busam, Klaus J
description Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.
doi_str_mv 10.1038/modpathol.2015.60
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4920599</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3764392111</sourcerecordid><originalsourceid>FETCH-LOGICAL-p267t-c96e4f0d1840d2d4a535e0adf4a679720ef2d1f0fc28d866e016b513ae98a7983</originalsourceid><addsrcrecordid>eNpdkU-LFDEQxYMo7rj6AbxIgxcvPVaSTjrxICyD_2DFi55DNqnMZO0ks-luYfHL2-OM6-qpCt6Px6t6hDynsKbA1etU_N5OuzKsGVCxlvCArKjg0AJT4iFZgdK85VqwM_JkHK8BaCcUe0zOmATGOsFX5OdmnmzGMo_NeDPbdFhs9k3GuRbMvrgaMzbOVhdzSfZNs8WMU3R2GG5_kzGlOZddHKfidphOio8hYMU8NaGW1HzG-h2HxuEw_PV6Sh4FO4z47DTPybf3775uPraXXz582lxctnsm-6l1WmIXwFPVgWe-s4ILBOtDZ2WvewYYmKcBgmPKKykRqLwSlFvUyvZa8XPy9ui7n68SerekqnYw-xqTrbem2Gj-VXLcmW35YTrNQGi9GLw6GdRyM-M4mRTHwy3HzxnaSyV6DSAX9OV_6HWZa17OWygAzqGXdKFe3E90F-VPLwvAjsC4SHmL9Z4NmEP55q58cyjfSOC_AHeOpoQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1700330761</pqid></control><display><type>article</type><title>Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>ProQuest Central UK/Ireland</source><source>Alma/SFX Local Collection</source><creator>Pulitzer, Melissa P ; Brannon, A Rose ; Berger, Michael F ; Louis, Peter ; Scott, Sasinya N ; Jungbluth, Achim A ; Coit, Daniel G ; Brownell, Isaac ; Busam, Klaus J</creator><creatorcontrib>Pulitzer, Melissa P ; Brannon, A Rose ; Berger, Michael F ; Louis, Peter ; Scott, Sasinya N ; Jungbluth, Achim A ; Coit, Daniel G ; Brownell, Isaac ; Busam, Klaus J</creatorcontrib><description>Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2015.60</identifier><identifier>PMID: 26022453</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>38/47 ; 692/53/2421 ; 82 ; 82/51 ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Carcinoma, Merkel Cell - chemistry ; Carcinoma, Merkel Cell - ethnology ; Carcinoma, Merkel Cell - genetics ; Carcinoma, Merkel Cell - pathology ; Carcinoma, Squamous Cell - chemistry ; Carcinoma, Squamous Cell - ethnology ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; DNA Mutational Analysis ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Keratin-20 - analysis ; Laboratory Medicine ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Mutation ; Neoplasms, Complex and Mixed - chemistry ; Neoplasms, Complex and Mixed - ethnology ; Neoplasms, Complex and Mixed - genetics ; Neoplasms, Complex and Mixed - pathology ; Neurofilament Proteins - analysis ; original-article ; Pathology ; Phenotype ; Polyomavirus ; Predictive Value of Tests ; Retinoblastoma Protein - analysis ; Retinoblastoma Protein - genetics ; Skin Neoplasms - chemistry ; Skin Neoplasms - ethnology ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Transcription Factors - analysis ; Tumor Suppressor Protein p53 - analysis ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Proteins - analysis ; White People - genetics</subject><ispartof>Modern pathology, 2015-08, Vol.28 (8), p.1023-1032</ispartof><rights>United States &amp; Canadian Academy of Pathology 2015</rights><rights>Copyright Nature Publishing Group Aug 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p267t-c96e4f0d1840d2d4a535e0adf4a679720ef2d1f0fc28d866e016b513ae98a7983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1700330761?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26022453$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pulitzer, Melissa P</creatorcontrib><creatorcontrib>Brannon, A Rose</creatorcontrib><creatorcontrib>Berger, Michael F</creatorcontrib><creatorcontrib>Louis, Peter</creatorcontrib><creatorcontrib>Scott, Sasinya N</creatorcontrib><creatorcontrib>Jungbluth, Achim A</creatorcontrib><creatorcontrib>Coit, Daniel G</creatorcontrib><creatorcontrib>Brownell, Isaac</creatorcontrib><creatorcontrib>Busam, Klaus J</creatorcontrib><title>Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.</description><subject>38/47</subject><subject>692/53/2421</subject><subject>82</subject><subject>82/51</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Carcinoma, Merkel Cell - chemistry</subject><subject>Carcinoma, Merkel Cell - ethnology</subject><subject>Carcinoma, Merkel Cell - genetics</subject><subject>Carcinoma, Merkel Cell - pathology</subject><subject>Carcinoma, Squamous Cell - chemistry</subject><subject>Carcinoma, Squamous Cell - ethnology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Genotype</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Keratin-20 - analysis</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasms, Complex and Mixed - chemistry</subject><subject>Neoplasms, Complex and Mixed - ethnology</subject><subject>Neoplasms, Complex and Mixed - genetics</subject><subject>Neoplasms, Complex and Mixed - pathology</subject><subject>Neurofilament Proteins - analysis</subject><subject>original-article</subject><subject>Pathology</subject><subject>Phenotype</subject><subject>Polyomavirus</subject><subject>Predictive Value of Tests</subject><subject>Retinoblastoma Protein - analysis</subject><subject>Retinoblastoma Protein - genetics</subject><subject>Skin Neoplasms - chemistry</subject><subject>Skin Neoplasms - ethnology</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Transcription Factors - analysis</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Proteins - analysis</subject><subject>White People - genetics</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkU-LFDEQxYMo7rj6AbxIgxcvPVaSTjrxICyD_2DFi55DNqnMZO0ks-luYfHL2-OM6-qpCt6Px6t6hDynsKbA1etU_N5OuzKsGVCxlvCArKjg0AJT4iFZgdK85VqwM_JkHK8BaCcUe0zOmATGOsFX5OdmnmzGMo_NeDPbdFhs9k3GuRbMvrgaMzbOVhdzSfZNs8WMU3R2GG5_kzGlOZddHKfidphOio8hYMU8NaGW1HzG-h2HxuEw_PV6Sh4FO4z47DTPybf3775uPraXXz582lxctnsm-6l1WmIXwFPVgWe-s4ILBOtDZ2WvewYYmKcBgmPKKykRqLwSlFvUyvZa8XPy9ui7n68SerekqnYw-xqTrbem2Gj-VXLcmW35YTrNQGi9GLw6GdRyM-M4mRTHwy3HzxnaSyV6DSAX9OV_6HWZa17OWygAzqGXdKFe3E90F-VPLwvAjsC4SHmL9Z4NmEP55q58cyjfSOC_AHeOpoQ</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Pulitzer, Melissa P</creator><creator>Brannon, A Rose</creator><creator>Berger, Michael F</creator><creator>Louis, Peter</creator><creator>Scott, Sasinya N</creator><creator>Jungbluth, Achim A</creator><creator>Coit, Daniel G</creator><creator>Brownell, Isaac</creator><creator>Busam, Klaus J</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20150801</creationdate><title>Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma</title><author>Pulitzer, Melissa P ; Brannon, A Rose ; Berger, Michael F ; Louis, Peter ; Scott, Sasinya N ; Jungbluth, Achim A ; Coit, Daniel G ; Brownell, Isaac ; Busam, Klaus J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p267t-c96e4f0d1840d2d4a535e0adf4a679720ef2d1f0fc28d866e016b513ae98a7983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>38/47</topic><topic>692/53/2421</topic><topic>82</topic><topic>82/51</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Carcinoma, Merkel Cell - chemistry</topic><topic>Carcinoma, Merkel Cell - ethnology</topic><topic>Carcinoma, Merkel Cell - genetics</topic><topic>Carcinoma, Merkel Cell - pathology</topic><topic>Carcinoma, Squamous Cell - chemistry</topic><topic>Carcinoma, Squamous Cell - ethnology</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>Genotype</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Keratin-20 - analysis</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasms, Complex and Mixed - chemistry</topic><topic>Neoplasms, Complex and Mixed - ethnology</topic><topic>Neoplasms, Complex and Mixed - genetics</topic><topic>Neoplasms, Complex and Mixed - pathology</topic><topic>Neurofilament Proteins - analysis</topic><topic>original-article</topic><topic>Pathology</topic><topic>Phenotype</topic><topic>Polyomavirus</topic><topic>Predictive Value of Tests</topic><topic>Retinoblastoma Protein - analysis</topic><topic>Retinoblastoma Protein - genetics</topic><topic>Skin Neoplasms - chemistry</topic><topic>Skin Neoplasms - ethnology</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - pathology</topic><topic>Transcription Factors - analysis</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Proteins - analysis</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pulitzer, Melissa P</creatorcontrib><creatorcontrib>Brannon, A Rose</creatorcontrib><creatorcontrib>Berger, Michael F</creatorcontrib><creatorcontrib>Louis, Peter</creatorcontrib><creatorcontrib>Scott, Sasinya N</creatorcontrib><creatorcontrib>Jungbluth, Achim A</creatorcontrib><creatorcontrib>Coit, Daniel G</creatorcontrib><creatorcontrib>Brownell, Isaac</creatorcontrib><creatorcontrib>Busam, Klaus J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pulitzer, Melissa P</au><au>Brannon, A Rose</au><au>Berger, Michael F</au><au>Louis, Peter</au><au>Scott, Sasinya N</au><au>Jungbluth, Achim A</au><au>Coit, Daniel G</au><au>Brownell, Isaac</au><au>Busam, Klaus J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>28</volume><issue>8</issue><spage>1023</spage><epage>1032</epage><pages>1023-1032</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26022453</pmid><doi>10.1038/modpathol.2015.60</doi><tpages>10</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0893-3952
ispartof Modern pathology, 2015-08, Vol.28 (8), p.1023-1032
issn 0893-3952
1530-0285
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4920599
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection
subjects 38/47
692/53/2421
82
82/51
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Carcinoma, Merkel Cell - chemistry
Carcinoma, Merkel Cell - ethnology
Carcinoma, Merkel Cell - genetics
Carcinoma, Merkel Cell - pathology
Carcinoma, Squamous Cell - chemistry
Carcinoma, Squamous Cell - ethnology
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
DNA Mutational Analysis
Female
Genotype
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Keratin-20 - analysis
Laboratory Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neoplasms, Complex and Mixed - chemistry
Neoplasms, Complex and Mixed - ethnology
Neoplasms, Complex and Mixed - genetics
Neoplasms, Complex and Mixed - pathology
Neurofilament Proteins - analysis
original-article
Pathology
Phenotype
Polyomavirus
Predictive Value of Tests
Retinoblastoma Protein - analysis
Retinoblastoma Protein - genetics
Skin Neoplasms - chemistry
Skin Neoplasms - ethnology
Skin Neoplasms - genetics
Skin Neoplasms - pathology
Transcription Factors - analysis
Tumor Suppressor Protein p53 - analysis
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Proteins - analysis
White People - genetics
title Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T20%3A03%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cutaneous%20squamous%20and%20neuroendocrine%20carcinoma:%20genetically%20and%20immunohistochemically%20different%20from%20Merkel%20cell%20carcinoma&rft.jtitle=Modern%20pathology&rft.au=Pulitzer,%20Melissa%20P&rft.date=2015-08-01&rft.volume=28&rft.issue=8&rft.spage=1023&rft.epage=1032&rft.pages=1023-1032&rft.issn=0893-3952&rft.eissn=1530-0285&rft.coden=MODPEO&rft_id=info:doi/10.1038/modpathol.2015.60&rft_dat=%3Cproquest_pubme%3E3764392111%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1700330761&rft_id=info:pmid/26022453&rfr_iscdi=true