Plasma cells in primary melanoma. Prognostic significance and possible role of IgA
Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma ce...
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creator | Bosisio, Francesca M Wilmott, James S Volders, Nathalie Mercier, Marjorie Wouters, Jasper Stas, Marguerite Blokx, Willeke AM Massi, Daniela Thompson, John F Scolyer, Richard A van Baren, Nicolas van den Oord, Joost J |
description | Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (
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doi_str_mv | 10.1038/modpathol.2016.28 |
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P
<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (
P
=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2016.28</identifier><identifier>PMID: 26867783</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/51 ; 14/63 ; 38/90 ; 38/91 ; 692/53/2422 ; 82/51 ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cancer ; Child ; Female ; Humans ; Immunoglobulin A ; Immunohistochemistry ; Kaplan-Meier Estimate ; Laboratory Medicine ; Lymphatic system ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Medical prognosis ; Medical research ; Medicine ; Medicine & Public Health ; Melanoma ; Melanoma - immunology ; Melanoma - mortality ; Melanoma - pathology ; Metastasis ; Middle Aged ; Oncology ; original-article ; Pathology ; Plasma ; Plasma Cells - immunology ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Skin Neoplasms - immunology ; Skin Neoplasms - mortality ; Skin Neoplasms - pathology ; Survival analysis ; Young Adult</subject><ispartof>Modern pathology, 2016-04, Vol.29 (4), p.347-358</ispartof><rights>United States & Canadian Academy of Pathology 2016</rights><rights>Copyright Nature Publishing Group Apr 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-c9090cb60cae920cda7ce8806b23e83d8d746aab0945c0755588f5a94c9916d03</citedby><cites>FETCH-LOGICAL-c415t-c9090cb60cae920cda7ce8806b23e83d8d746aab0945c0755588f5a94c9916d03</cites><orcidid>0000-0002-7129-2990</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1776373665?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26867783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bosisio, Francesca M</creatorcontrib><creatorcontrib>Wilmott, James S</creatorcontrib><creatorcontrib>Volders, Nathalie</creatorcontrib><creatorcontrib>Mercier, Marjorie</creatorcontrib><creatorcontrib>Wouters, Jasper</creatorcontrib><creatorcontrib>Stas, Marguerite</creatorcontrib><creatorcontrib>Blokx, Willeke AM</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Thompson, John F</creatorcontrib><creatorcontrib>Scolyer, Richard A</creatorcontrib><creatorcontrib>van Baren, Nicolas</creatorcontrib><creatorcontrib>van den Oord, Joost J</creatorcontrib><title>Plasma cells in primary melanoma. Prognostic significance and possible role of IgA</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (
P
<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (
P
=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.</description><subject>13/51</subject><subject>14/63</subject><subject>38/90</subject><subject>38/91</subject><subject>692/53/2422</subject><subject>82/51</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer</subject><subject>Child</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin A</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Laboratory Medicine</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melanoma</subject><subject>Melanoma - immunology</subject><subject>Melanoma - mortality</subject><subject>Melanoma - pathology</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pathology</subject><subject>Plasma</subject><subject>Plasma Cells - immunology</subject><subject>Prognosis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - mortality</subject><subject>Skin Neoplasms - pathology</subject><subject>Survival analysis</subject><subject>Young Adult</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</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>eNp1kE1LAzEQhoMotn78AC8S8OJl6yTZfB1L8QsKiuh5yWazdctuUpP24L83pVVE8JI55Jl3Zh6ELghMCDB1M4RmZdbvoZ9QIGJC1QEaE86gAKr4IRqD0qxgmtMROklpCUBKrugxGlGhhJSKjdHLc2_SYLB1fZ9w5_EqdoOJn3hwvfFhMBP8HMPCh7TuLE7dwndtZ423Dhvf4FVIqat7h2PIT2jx42J6ho5a0yd3vq-n6O3u9nX2UMyf7h9n03lhS8LXhdWgwdYCrHGagm2MtE4pEDVlTrFGNbIUxtSgS25Bcs6VarnRpdWaiAbYKbre5a5i-Ni4tK6GLm3vMN6FTaqIlBJkjtYZvfqDLsMm-rzdlhJMMiF4psiOsjGfFV1b7WVUBKqt8OpHeLUVXlGVey73yZt6cM1Px7fhDNAdkPKXX7j4a_S_qV88147C</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Bosisio, Francesca M</creator><creator>Wilmott, James S</creator><creator>Volders, Nathalie</creator><creator>Mercier, Marjorie</creator><creator>Wouters, Jasper</creator><creator>Stas, Marguerite</creator><creator>Blokx, Willeke AM</creator><creator>Massi, Daniela</creator><creator>Thompson, John F</creator><creator>Scolyer, Richard A</creator><creator>van Baren, Nicolas</creator><creator>van den Oord, Joost 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>AAYXX</scope><scope>CITATION</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>7X8</scope><orcidid>https://orcid.org/0000-0002-7129-2990</orcidid></search><sort><creationdate>20160401</creationdate><title>Plasma cells in primary melanoma. Prognostic significance and possible role of IgA</title><author>Bosisio, Francesca M ; Wilmott, James S ; Volders, Nathalie ; Mercier, Marjorie ; Wouters, Jasper ; Stas, Marguerite ; Blokx, Willeke AM ; Massi, Daniela ; Thompson, John F ; Scolyer, Richard A ; van Baren, Nicolas ; van den Oord, Joost J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-c9090cb60cae920cda7ce8806b23e83d8d746aab0945c0755588f5a94c9916d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/51</topic><topic>14/63</topic><topic>38/90</topic><topic>38/91</topic><topic>692/53/2422</topic><topic>82/51</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer</topic><topic>Child</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin A</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Laboratory Medicine</topic><topic>Lymphatic system</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melanoma</topic><topic>Melanoma - immunology</topic><topic>Melanoma - mortality</topic><topic>Melanoma - pathology</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>original-article</topic><topic>Pathology</topic><topic>Plasma</topic><topic>Plasma Cells - immunology</topic><topic>Prognosis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - mortality</topic><topic>Skin Neoplasms - pathology</topic><topic>Survival analysis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bosisio, Francesca M</creatorcontrib><creatorcontrib>Wilmott, James S</creatorcontrib><creatorcontrib>Volders, Nathalie</creatorcontrib><creatorcontrib>Mercier, Marjorie</creatorcontrib><creatorcontrib>Wouters, Jasper</creatorcontrib><creatorcontrib>Stas, Marguerite</creatorcontrib><creatorcontrib>Blokx, Willeke AM</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Thompson, John F</creatorcontrib><creatorcontrib>Scolyer, Richard A</creatorcontrib><creatorcontrib>van Baren, Nicolas</creatorcontrib><creatorcontrib>van den Oord, Joost J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & 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 & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & 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>MEDLINE - Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bosisio, Francesca M</au><au>Wilmott, James S</au><au>Volders, Nathalie</au><au>Mercier, Marjorie</au><au>Wouters, Jasper</au><au>Stas, Marguerite</au><au>Blokx, Willeke AM</au><au>Massi, Daniela</au><au>Thompson, John F</au><au>Scolyer, Richard A</au><au>van Baren, Nicolas</au><au>van den Oord, Joost J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma cells in primary melanoma. Prognostic significance and possible role of IgA</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>29</volume><issue>4</issue><spage>347</spage><epage>358</epage><pages>347-358</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (
P
<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (
P
=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26867783</pmid><doi>10.1038/modpathol.2016.28</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-7129-2990</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 13/51 14/63 38/90 38/91 692/53/2422 82/51 Adolescent Adult Aged Aged, 80 and over Cancer Child Female Humans Immunoglobulin A Immunohistochemistry Kaplan-Meier Estimate Laboratory Medicine Lymphatic system Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Male Medical prognosis Medical research Medicine Medicine & Public Health Melanoma Melanoma - immunology Melanoma - mortality Melanoma - pathology Metastasis Middle Aged Oncology original-article Pathology Plasma Plasma Cells - immunology Prognosis Reverse Transcriptase Polymerase Chain Reaction Skin Neoplasms - immunology Skin Neoplasms - mortality Skin Neoplasms - pathology Survival analysis Young Adult |
title | Plasma cells in primary melanoma. Prognostic significance and possible role of IgA |
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