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Associations Between Loss of ARID1A Expression and Clinicopathologic and Genetic Variables in T1 Early Colorectal Cancer

Abstract Objectives To evaluate the relationships between adenine-thymine-rich interactive domain 1A (ARID1A) expression and the clinicopathologic features in T1 colorectal cancer (CRC) and to investigate whether the presence of ARID1A protein is related to genetic changes. Methods We retrospectivel...

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Published in:American journal of clinical pathology 2019-09, Vol.152 (4), p.463-470
Main Authors: Kishida, Yoshihiro, Oishi, Takuma, Sugino, Takashi, Shiomi, Akio, Urakami, Kenichi, Kusuhara, Masatoshi, Yamaguchi, Ken, Kitagawa, Yuko, Ono, Hiroyuki
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creator Kishida, Yoshihiro
Oishi, Takuma
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Kitagawa, Yuko
Ono, Hiroyuki
description Abstract Objectives To evaluate the relationships between adenine-thymine-rich interactive domain 1A (ARID1A) expression and the clinicopathologic features in T1 colorectal cancer (CRC) and to investigate whether the presence of ARID1A protein is related to genetic changes. Methods We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated. The relationship between ARID1A expression and 409 cancer-related gene mutations was also evaluated using next-generation sequencing (NGS). Results Immunohistochemical staining indicated negative ARID1A expression in 4.6%. Loss of ARID1A expression was significantly associated with younger age, lymphatic invasion, and lymph node metastasis (LNM). NGS showed that PKHD1, RNF213, and MSH6 mutations were more frequent in ARID1A-negative tumors, whereas KRAS mutations were more common in ARID1A-positive tumors. Conclusions In T1 CRC, negative ARID1A expression was correlated with early onset, lymphatic invasion, and LNM. Mutations in some cancer-related genes were possibly related with ARID1A expression.
doi_str_mv 10.1093/ajcp/aqz062
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Methods We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated. The relationship between ARID1A expression and 409 cancer-related gene mutations was also evaluated using next-generation sequencing (NGS). Results Immunohistochemical staining indicated negative ARID1A expression in 4.6%. Loss of ARID1A expression was significantly associated with younger age, lymphatic invasion, and lymph node metastasis (LNM). NGS showed that PKHD1, RNF213, and MSH6 mutations were more frequent in ARID1A-negative tumors, whereas KRAS mutations were more common in ARID1A-positive tumors. Conclusions In T1 CRC, negative ARID1A expression was correlated with early onset, lymphatic invasion, and LNM. Mutations in some cancer-related genes were possibly related with ARID1A expression.</description><identifier>ISSN: 0002-9173</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1093/ajcp/aqz062</identifier><identifier>PMID: 31263894</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adenine ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cancer ; Care and treatment ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Development and progression ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Drosophila Proteins ; Female ; Gene expression ; Genetic aspects ; Genetic variation ; Health aspects ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Lymph nodes ; Lymphatic Metastasis - genetics ; Lymphatic Metastasis - pathology ; Male ; Membrane Proteins ; Metastases ; Middle Aged ; MSH6 protein ; Mutation ; Next-generation sequencing ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; Retrospective Studies ; Thymine ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumors</subject><ispartof>American journal of clinical pathology, 2019-09, Vol.152 (4), p.463-470</ispartof><rights>American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019</rights><rights>American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-f3c1f650b9bff188af099f23acaa2952731a4fb45429b0d583c6eb09cef2abf53</citedby><cites>FETCH-LOGICAL-c481t-f3c1f650b9bff188af099f23acaa2952731a4fb45429b0d583c6eb09cef2abf53</cites><orcidid>0000-0002-5068-6990 ; 0000-0002-8215-1720</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31263894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kishida, Yoshihiro</creatorcontrib><creatorcontrib>Oishi, Takuma</creatorcontrib><creatorcontrib>Sugino, Takashi</creatorcontrib><creatorcontrib>Shiomi, Akio</creatorcontrib><creatorcontrib>Urakami, Kenichi</creatorcontrib><creatorcontrib>Kusuhara, Masatoshi</creatorcontrib><creatorcontrib>Yamaguchi, Ken</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Ono, Hiroyuki</creatorcontrib><title>Associations Between Loss of ARID1A Expression and Clinicopathologic and Genetic Variables in T1 Early Colorectal Cancer</title><title>American journal of clinical pathology</title><addtitle>Am J Clin Pathol</addtitle><description>Abstract Objectives To evaluate the relationships between adenine-thymine-rich interactive domain 1A (ARID1A) expression and the clinicopathologic features in T1 colorectal cancer (CRC) and to investigate whether the presence of ARID1A protein is related to genetic changes. Methods We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated. The relationship between ARID1A expression and 409 cancer-related gene mutations was also evaluated using next-generation sequencing (NGS). Results Immunohistochemical staining indicated negative ARID1A expression in 4.6%. Loss of ARID1A expression was significantly associated with younger age, lymphatic invasion, and lymph node metastasis (LNM). NGS showed that PKHD1, RNF213, and MSH6 mutations were more frequent in ARID1A-negative tumors, whereas KRAS mutations were more common in ARID1A-positive tumors. Conclusions In T1 CRC, negative ARID1A expression was correlated with early onset, lymphatic invasion, and LNM. Mutations in some cancer-related genes were possibly related with ARID1A expression.</description><subject>Adenine</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Development and progression</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drosophila Proteins</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic variation</subject><subject>Health aspects</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis - genetics</subject><subject>Lymphatic Metastasis - pathology</subject><subject>Male</subject><subject>Membrane Proteins</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>MSH6 protein</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>Retrospective Studies</subject><subject>Thymine</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumors</subject><issn>0002-9173</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1rFEEQxQdRzCZ68i4NggRkkv6ajz5O1jUGFgSJXpua3urYy2z3pHsGE_96e92oKCJ1qKL41aN4ryheMHrGqBLnsDXjOdx-ozV_VCyYkqJsGs4fFwtKKS8Va8RRcZzSllLGWyqfFkeC8Vq0Si6Kuy6lYBxMLvhELnD6iujJOqREgiXdx6u3rCOruzFiShkh4DdkOTjvTBhh-hKGcOPMj-0lepzy_Bmig37ARJwn14ysIA73ZJnJiGaCgSzBG4zPiicWhoTPH_pJ8end6nr5vlx_uLxaduvSyJZNpRWG2bqiveqtZW0LlipluQADwFXFG8FA2l5WkquebqpWmBp7qgxaDr2txElxetAdY7idMU1655LBYQCPYU6a84oxWjVNk9FXf6HbMEefv9NcCMUqKSX7Td3AgNp5G6YIZi-qu1q22VZRq0yd_YPKtcFd9s6jdXn_x8Gbw4GJ2fyIVo_R7SDea0b1Pme9z1kfcs70y4dX536Hm1_sz2Az8PoAhHn8r9J38Yev7Q</recordid><startdate>20190909</startdate><enddate>20190909</enddate><creator>Kishida, Yoshihiro</creator><creator>Oishi, Takuma</creator><creator>Sugino, Takashi</creator><creator>Shiomi, Akio</creator><creator>Urakami, Kenichi</creator><creator>Kusuhara, Masatoshi</creator><creator>Yamaguchi, Ken</creator><creator>Kitagawa, Yuko</creator><creator>Ono, Hiroyuki</creator><general>Oxford University Press</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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><orcidid>https://orcid.org/0000-0002-5068-6990</orcidid><orcidid>https://orcid.org/0000-0002-8215-1720</orcidid></search><sort><creationdate>20190909</creationdate><title>Associations Between Loss of ARID1A Expression and Clinicopathologic and Genetic Variables in T1 Early Colorectal Cancer</title><author>Kishida, Yoshihiro ; 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Methods We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated. The relationship between ARID1A expression and 409 cancer-related gene mutations was also evaluated using next-generation sequencing (NGS). Results Immunohistochemical staining indicated negative ARID1A expression in 4.6%. Loss of ARID1A expression was significantly associated with younger age, lymphatic invasion, and lymph node metastasis (LNM). NGS showed that PKHD1, RNF213, and MSH6 mutations were more frequent in ARID1A-negative tumors, whereas KRAS mutations were more common in ARID1A-positive tumors. Conclusions In T1 CRC, negative ARID1A expression was correlated with early onset, lymphatic invasion, and LNM. Mutations in some cancer-related genes were possibly related with ARID1A expression.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>31263894</pmid><doi>10.1093/ajcp/aqz062</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5068-6990</orcidid><orcidid>https://orcid.org/0000-0002-8215-1720</orcidid></addata></record>
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subjects Adenine
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adult
Age Factors
Aged
Aged, 80 and over
Cancer
Care and treatment
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Development and progression
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Drosophila Proteins
Female
Gene expression
Genetic aspects
Genetic variation
Health aspects
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Lymph nodes
Lymphatic Metastasis - genetics
Lymphatic Metastasis - pathology
Male
Membrane Proteins
Metastases
Middle Aged
MSH6 protein
Mutation
Next-generation sequencing
Proto-Oncogene Proteins p21(ras) - genetics
Proto-Oncogene Proteins p21(ras) - metabolism
Retrospective Studies
Thymine
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
Tumors
title Associations Between Loss of ARID1A Expression and Clinicopathologic and Genetic Variables in T1 Early Colorectal Cancer
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