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Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma
The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC. This study inclu...
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Published in: | Pathology, research and practice research and practice, 2015-02, Vol.211 (2), p.162-170 |
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container_title | Pathology, research and practice |
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description | The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC.
This study included 467 patients with PTC who underwent surgical resection. We studied the BRAFV600E mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).
The frequencies of a positive BRAFV600E mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAFV600E mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAFV600E mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P |
doi_str_mv | 10.1016/j.prp.2014.10.005 |
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This study included 467 patients with PTC who underwent surgical resection. We studied the BRAFV600E mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).
The frequencies of a positive BRAFV600E mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAFV600E mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAFV600E mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAFV600E mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant.
Our results showed that positive BRAF V600E IHC significantly correlated with the BRAFV600E mutation. This suggests its clinical utility as a screening tool for the BRAFV600E mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAFV600E mutation-positive cases of PTC.</description><identifier>ISSN: 0344-0338</identifier><identifier>EISSN: 1618-0631</identifier><identifier>DOI: 10.1016/j.prp.2014.10.005</identifier><identifier>PMID: 25468810</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Adolescent ; Adult ; Aged ; Biomarkers, Tumor - genetics ; BRAF V600E mutation ; Carcinoma - genetics ; Carcinoma - pathology ; Carcinoma, Papillary ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Papillary carcinoma ; Prognosis ; Proto-Oncogene Proteins B-raf - genetics ; Real-Time Polymerase Chain Reaction ; RNA - analysis ; RNA in situ hybridization ; Sensitivity and Specificity ; Thyroid Cancer, Papillary ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - pathology ; Tissue Array Analysis ; Young Adult</subject><ispartof>Pathology, research and practice, 2015-02, Vol.211 (2), p.162-170</ispartof><rights>2014 Elsevier GmbH</rights><rights>Copyright © 2014 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c268t-9919419769d5ac3a6029257ce8e48bd398770a2423e3b616bc511f00a11f4b953</citedby><cites>FETCH-LOGICAL-c268t-9919419769d5ac3a6029257ce8e48bd398770a2423e3b616bc511f00a11f4b953</cites></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/25468810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Yoon Yang</creatorcontrib><creatorcontrib>Yoo, Jae Hyung</creatorcontrib><creatorcontrib>Park, Eon Sub</creatorcontrib><creatorcontrib>Kim, Mi Kyung</creatorcontrib><creatorcontrib>Lee, Tae Jin</creatorcontrib><creatorcontrib>Cho, Bo Youn</creatorcontrib><creatorcontrib>Chung, Yun Jae</creatorcontrib><creatorcontrib>Kang, Kyung Ho</creatorcontrib><creatorcontrib>Ahn, Hwa Young</creatorcontrib><creatorcontrib>Kim, Hee Sung</creatorcontrib><title>Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma</title><title>Pathology, research and practice</title><addtitle>Pathol Res Pract</addtitle><description>The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC.
This study included 467 patients with PTC who underwent surgical resection. We studied the BRAFV600E mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).
The frequencies of a positive BRAFV600E mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAFV600E mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAFV600E mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAFV600E mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant.
Our results showed that positive BRAF V600E IHC significantly correlated with the BRAFV600E mutation. This suggests its clinical utility as a screening tool for the BRAFV600E mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAFV600E mutation-positive cases of PTC.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>BRAF V600E mutation</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - pathology</subject><subject>Carcinoma, Papillary</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Papillary carcinoma</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA - analysis</subject><subject>RNA in situ hybridization</subject><subject>Sensitivity and Specificity</subject><subject>Thyroid Cancer, Papillary</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Tissue Array Analysis</subject><subject>Young Adult</subject><issn>0344-0338</issn><issn>1618-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAQhi1ERbeFB-CCfOTQbMd27DjitKxaQKqKVAFXy3G8xKskDraDtDwLD1vvpnDsxSN__uf3jH6E3hJYEyDier-ewrSmQMp8XwPwF2hFBJEFCEZeohWwsiyAMXmOLmLcA0AFJXmFzikvhZQEVujvtnejM37SqfO9_-kMNj4E2-vk_Bix3-HUWfzxYXP7QwDc4GFOp6erE8MLdMMwj75zMXnT2SHXcLjCemwX0cP9BrsRR5dm3B2a4Fr352RypJOeXN_rcMgfHYJ3LTY6GDf6Qb9GZzvdR_vmqV6i77c337afi7uvn75sN3eFoUKmoq5JXZK6EnXLtWFaAK0pr4yVtpRNy2pZVaBpSZlljSCiMZyQHYDOZ9nUnF2i94vvFPyv2cak8grG5qlG6-eoiOCcU0alzFKySE3wMQa7U1NwQ55eEVDHUNQ-k0kdQzmiHEruefdkPzeDbf93_EshCz4sApuX_O1sUNE4OxrbumBNUq13z9g_AoL6nKY</recordid><startdate>201502</startdate><enddate>201502</enddate><creator>Jung, Yoon Yang</creator><creator>Yoo, Jae Hyung</creator><creator>Park, Eon Sub</creator><creator>Kim, Mi Kyung</creator><creator>Lee, Tae Jin</creator><creator>Cho, Bo Youn</creator><creator>Chung, Yun Jae</creator><creator>Kang, Kyung Ho</creator><creator>Ahn, Hwa Young</creator><creator>Kim, Hee Sung</creator><general>Elsevier GmbH</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>7X8</scope></search><sort><creationdate>201502</creationdate><title>Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma</title><author>Jung, Yoon Yang ; Yoo, Jae Hyung ; Park, Eon Sub ; Kim, Mi Kyung ; Lee, Tae Jin ; Cho, Bo Youn ; Chung, Yun Jae ; Kang, Kyung Ho ; Ahn, Hwa Young ; Kim, Hee Sung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c268t-9919419769d5ac3a6029257ce8e48bd398770a2423e3b616bc511f00a11f4b953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>BRAF V600E mutation</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - pathology</topic><topic>Carcinoma, Papillary</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Papillary carcinoma</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA - analysis</topic><topic>RNA in situ hybridization</topic><topic>Sensitivity and Specificity</topic><topic>Thyroid Cancer, Papillary</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Tissue Array Analysis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jung, Yoon Yang</creatorcontrib><creatorcontrib>Yoo, Jae Hyung</creatorcontrib><creatorcontrib>Park, Eon Sub</creatorcontrib><creatorcontrib>Kim, Mi Kyung</creatorcontrib><creatorcontrib>Lee, Tae Jin</creatorcontrib><creatorcontrib>Cho, Bo Youn</creatorcontrib><creatorcontrib>Chung, Yun Jae</creatorcontrib><creatorcontrib>Kang, Kyung Ho</creatorcontrib><creatorcontrib>Ahn, Hwa Young</creatorcontrib><creatorcontrib>Kim, Hee Sung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology, research and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jung, Yoon Yang</au><au>Yoo, Jae Hyung</au><au>Park, Eon Sub</au><au>Kim, Mi Kyung</au><au>Lee, Tae Jin</au><au>Cho, Bo Youn</au><au>Chung, Yun Jae</au><au>Kang, Kyung Ho</au><au>Ahn, Hwa Young</au><au>Kim, Hee Sung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma</atitle><jtitle>Pathology, research and practice</jtitle><addtitle>Pathol Res Pract</addtitle><date>2015-02</date><risdate>2015</risdate><volume>211</volume><issue>2</issue><spage>162</spage><epage>170</epage><pages>162-170</pages><issn>0344-0338</issn><eissn>1618-0631</eissn><abstract>The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC.
This study included 467 patients with PTC who underwent surgical resection. We studied the BRAFV600E mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).
The frequencies of a positive BRAFV600E mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAFV600E mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAFV600E mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAFV600E mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant.
Our results showed that positive BRAF V600E IHC significantly correlated with the BRAFV600E mutation. This suggests its clinical utility as a screening tool for the BRAFV600E mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAFV600E mutation-positive cases of PTC.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>25468810</pmid><doi>10.1016/j.prp.2014.10.005</doi><tpages>9</tpages></addata></record> |
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subjects | Adolescent Adult Aged Biomarkers, Tumor - genetics BRAF V600E mutation Carcinoma - genetics Carcinoma - pathology Carcinoma, Papillary Female Humans Immunohistochemistry In Situ Hybridization Lymphatic Metastasis Male Middle Aged Mutation Papillary carcinoma Prognosis Proto-Oncogene Proteins B-raf - genetics Real-Time Polymerase Chain Reaction RNA - analysis RNA in situ hybridization Sensitivity and Specificity Thyroid Cancer, Papillary Thyroid Neoplasms - genetics Thyroid Neoplasms - pathology Tissue Array Analysis Young Adult |
title | Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma |
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