Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan
Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo an...
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creator | Tomita, Sakura Kikuti, Yara Y Carreras, Joaquim Kojima, Minoru Ando, Kiyoshi Takasaki, Hirotaka Sakai, Rika Takata, Katsuyoshi Yoshino, Tadashi Bea, Silvia Campo, Elias Nakamura, Naoya |
description | Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs
de novo
and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence
in situ
hybridization (FISH) at five different loci: 1q21.3 (
CKS1B
), 6q16.3 (
HACE1
), 7p22.3 (
MAFK
), 9q33.3 (
PPP6C
), and 9q34.3 (
ASS1
,
CARD9
) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2
+
(60%), CD3
ɛ
+
(100%), CD4
+
(10%), CD7
+
(95%), CD8
+
(80%), CD56
+
(85%), TIA-1
+
(100%), Granzyme B
+
(25%), T-cell receptor (TCR)
β
+
(10%), TCR
γ
+
(35%), TCR
γδ
+
(50%), and double negative for TCR (six cases, 30%). All cases were EBER
−
. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8
+
CD56
+
phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including
MYC
). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of
αβ
-T-cells and
γδ
-T-cells. |
doi_str_mv | 10.1038/modpathol.2015.85 |
format | Article |
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de novo
and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence
in situ
hybridization (FISH) at five different loci: 1q21.3 (
CKS1B
), 6q16.3 (
HACE1
), 7p22.3 (
MAFK
), 9q33.3 (
PPP6C
), and 9q34.3 (
ASS1
,
CARD9
) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2
+
(60%), CD3
ɛ
+
(100%), CD4
+
(10%), CD7
+
(95%), CD8
+
(80%), CD56
+
(85%), TIA-1
+
(100%), Granzyme B
+
(25%), T-cell receptor (TCR)
β
+
(10%), TCR
γ
+
(35%), TCR
γδ
+
(50%), and double negative for TCR (six cases, 30%). All cases were EBER
−
. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8
+
CD56
+
phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including
MYC
). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of
αβ
-T-cells and
γδ
-T-cells.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2015.85</identifier><identifier>PMID: 26226842</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>692/699/1541/1990/291/1621/1916 ; 82/51 ; Adult ; Aged ; Comparative Genomic Hybridization ; Enteropathy-Associated T-Cell Lymphoma - genetics ; Enteropathy-Associated T-Cell Lymphoma - immunology ; Enteropathy-Associated T-Cell Lymphoma - pathology ; Female ; Genome, Human ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Laboratory Medicine ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; original-article ; Pathology</subject><ispartof>Modern pathology, 2015-10, Vol.28 (10), p.1286-1296</ispartof><rights>United States & Canadian Academy of Pathology 2015</rights><rights>Copyright Nature Publishing Group Oct 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-97aef31e05f10aa0864a9cbab7c4fc6ec60508a6c736fbb4f4f1db53b8320c13</citedby><cites>FETCH-LOGICAL-c518t-97aef31e05f10aa0864a9cbab7c4fc6ec60508a6c736fbb4f4f1db53b8320c13</cites><orcidid>0000-0001-9850-9793</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1717465442?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,64390,64392,64394,72474</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26226842$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomita, Sakura</creatorcontrib><creatorcontrib>Kikuti, Yara Y</creatorcontrib><creatorcontrib>Carreras, Joaquim</creatorcontrib><creatorcontrib>Kojima, Minoru</creatorcontrib><creatorcontrib>Ando, Kiyoshi</creatorcontrib><creatorcontrib>Takasaki, Hirotaka</creatorcontrib><creatorcontrib>Sakai, Rika</creatorcontrib><creatorcontrib>Takata, Katsuyoshi</creatorcontrib><creatorcontrib>Yoshino, Tadashi</creatorcontrib><creatorcontrib>Bea, Silvia</creatorcontrib><creatorcontrib>Campo, Elias</creatorcontrib><creatorcontrib>Nakamura, Naoya</creatorcontrib><title>Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs
de novo
and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence
in situ
hybridization (FISH) at five different loci: 1q21.3 (
CKS1B
), 6q16.3 (
HACE1
), 7p22.3 (
MAFK
), 9q33.3 (
PPP6C
), and 9q34.3 (
ASS1
,
CARD9
) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2
+
(60%), CD3
ɛ
+
(100%), CD4
+
(10%), CD7
+
(95%), CD8
+
(80%), CD56
+
(85%), TIA-1
+
(100%), Granzyme B
+
(25%), T-cell receptor (TCR)
β
+
(10%), TCR
γ
+
(35%), TCR
γδ
+
(50%), and double negative for TCR (six cases, 30%). All cases were EBER
−
. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8
+
CD56
+
phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including
MYC
). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of
αβ
-T-cells and
γδ
-T-cells.</description><subject>692/699/1541/1990/291/1621/1916</subject><subject>82/51</subject><subject>Adult</subject><subject>Aged</subject><subject>Comparative Genomic Hybridization</subject><subject>Enteropathy-Associated T-Cell Lymphoma - genetics</subject><subject>Enteropathy-Associated T-Cell Lymphoma - immunology</subject><subject>Enteropathy-Associated T-Cell Lymphoma - pathology</subject><subject>Female</subject><subject>Genome, Human</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunophenotyping</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Japan</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>original-article</subject><subject>Pathology</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>eNqNkU1LxDAQhoMouq7-AC8S8OKla76bPYr4yYKXvXko0zRxK01Sm_aw_96WVRFB8DAMzDzzzgwvQmeULCjh-srHqoV-E5sFI1QutNxDMyo5yQjTch_NiF7yjC8lO0LHKb0RQoXU7BAdMcWY0oLN0Mu9DdHXBkOocO39EOKmTn00GztWocFtF13d2ISjwzb0tovTym0GKUVTQ28rvM6MbRrcbH27iR5wHfATtBBO0IGDJtnTzzxH67vb9c1Dtnq-f7y5XmVGUt1nyxys49QS6SgBIFoJWJoSytwIZ5Q1ikiiQZmcK1eWwglHq1LyUnNGDOVzdLmTHU99H2zqC1-n6SIINg6poDnLVU6VIP9AqeacizHm6OIX-haHLox_TFQulBSCjRTdUaaLKXXWFW1Xe-i2BSXF5FHx7VExeVRoOc6cfyoPpbfV98SXKSPAdkAaW-HVdj9W_6n6AdDkoUA</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Tomita, Sakura</creator><creator>Kikuti, Yara Y</creator><creator>Carreras, Joaquim</creator><creator>Kojima, Minoru</creator><creator>Ando, Kiyoshi</creator><creator>Takasaki, Hirotaka</creator><creator>Sakai, Rika</creator><creator>Takata, Katsuyoshi</creator><creator>Yoshino, Tadashi</creator><creator>Bea, Silvia</creator><creator>Campo, Elias</creator><creator>Nakamura, Naoya</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>PRINS</scope><scope>7X8</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0001-9850-9793</orcidid></search><sort><creationdate>20151001</creationdate><title>Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan</title><author>Tomita, Sakura ; Kikuti, Yara Y ; Carreras, Joaquim ; Kojima, Minoru ; Ando, Kiyoshi ; Takasaki, Hirotaka ; Sakai, Rika ; Takata, Katsuyoshi ; Yoshino, Tadashi ; Bea, Silvia ; Campo, Elias ; Nakamura, Naoya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-97aef31e05f10aa0864a9cbab7c4fc6ec60508a6c736fbb4f4f1db53b8320c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>692/699/1541/1990/291/1621/1916</topic><topic>82/51</topic><topic>Adult</topic><topic>Aged</topic><topic>Comparative Genomic Hybridization</topic><topic>Enteropathy-Associated T-Cell Lymphoma - genetics</topic><topic>Enteropathy-Associated T-Cell Lymphoma - immunology</topic><topic>Enteropathy-Associated T-Cell Lymphoma - pathology</topic><topic>Female</topic><topic>Genome, Human</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunophenotyping</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Japan</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>original-article</topic><topic>Pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomita, Sakura</creatorcontrib><creatorcontrib>Kikuti, Yara Y</creatorcontrib><creatorcontrib>Carreras, Joaquim</creatorcontrib><creatorcontrib>Kojima, Minoru</creatorcontrib><creatorcontrib>Ando, Kiyoshi</creatorcontrib><creatorcontrib>Takasaki, Hirotaka</creatorcontrib><creatorcontrib>Sakai, Rika</creatorcontrib><creatorcontrib>Takata, Katsuyoshi</creatorcontrib><creatorcontrib>Yoshino, Tadashi</creatorcontrib><creatorcontrib>Bea, Silvia</creatorcontrib><creatorcontrib>Campo, Elias</creatorcontrib><creatorcontrib>Nakamura, Naoya</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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tomita, Sakura</au><au>Kikuti, Yara Y</au><au>Carreras, Joaquim</au><au>Kojima, Minoru</au><au>Ando, Kiyoshi</au><au>Takasaki, Hirotaka</au><au>Sakai, Rika</au><au>Takata, Katsuyoshi</au><au>Yoshino, Tadashi</au><au>Bea, Silvia</au><au>Campo, Elias</au><au>Nakamura, Naoya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>28</volume><issue>10</issue><spage>1286</spage><epage>1296</epage><pages>1286-1296</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs
de novo
and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence
in situ
hybridization (FISH) at five different loci: 1q21.3 (
CKS1B
), 6q16.3 (
HACE1
), 7p22.3 (
MAFK
), 9q33.3 (
PPP6C
), and 9q34.3 (
ASS1
,
CARD9
) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2
+
(60%), CD3
ɛ
+
(100%), CD4
+
(10%), CD7
+
(95%), CD8
+
(80%), CD56
+
(85%), TIA-1
+
(100%), Granzyme B
+
(25%), T-cell receptor (TCR)
β
+
(10%), TCR
γ
+
(35%), TCR
γδ
+
(50%), and double negative for TCR (six cases, 30%). All cases were EBER
−
. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8
+
CD56
+
phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including
MYC
). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of
αβ
-T-cells and
γδ
-T-cells.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26226842</pmid><doi>10.1038/modpathol.2015.85</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9850-9793</orcidid><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
subjects | 692/699/1541/1990/291/1621/1916 82/51 Adult Aged Comparative Genomic Hybridization Enteropathy-Associated T-Cell Lymphoma - genetics Enteropathy-Associated T-Cell Lymphoma - immunology Enteropathy-Associated T-Cell Lymphoma - pathology Female Genome, Human Humans Immunohistochemistry Immunophenotyping In Situ Hybridization, Fluorescence Japan Laboratory Medicine Male Medicine Medicine & Public Health Middle Aged Oligonucleotide Array Sequence Analysis original-article Pathology |
title | Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan |
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