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Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy

Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy...

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Autores principales: Kim, Hyo Song, Shin, Su-Jin, Beom, Seung-Hoon, Jung, Minkyu, Choi, Yoon Young, Son, Taeil, Kim, Hyoung-Il, Cheong, Jae-Ho, Hyung, Woo Jin, Noh, Sung Hoon, Chung, Hyunsoo, Park, Jun Chul, Shin, Sung Kwan, Lee, Sang Kil, Lee, Yong Chan, Koom, Woong Sub, Lim, Joon Seok, Chung, Hyun Cheol, Rha, Sun Young, Kim, Hyunki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190122/
https://www.ncbi.nlm.nih.gov/pubmed/27331626
http://dx.doi.org/10.18632/oncotarget.10115
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author Kim, Hyo Song
Shin, Su-Jin
Beom, Seung-Hoon
Jung, Minkyu
Choi, Yoon Young
Son, Taeil
Kim, Hyoung-Il
Cheong, Jae-Ho
Hyung, Woo Jin
Noh, Sung Hoon
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Lee, Yong Chan
Koom, Woong Sub
Lim, Joon Seok
Chung, Hyun Cheol
Rha, Sun Young
Kim, Hyunki
author_facet Kim, Hyo Song
Shin, Su-Jin
Beom, Seung-Hoon
Jung, Minkyu
Choi, Yoon Young
Son, Taeil
Kim, Hyoung-Il
Cheong, Jae-Ho
Hyung, Woo Jin
Noh, Sung Hoon
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Lee, Yong Chan
Koom, Woong Sub
Lim, Joon Seok
Chung, Hyun Cheol
Rha, Sun Young
Kim, Hyunki
author_sort Kim, Hyo Song
collection PubMed
description Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials.
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spelling pubmed-51901222017-01-05 Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy Kim, Hyo Song Shin, Su-Jin Beom, Seung-Hoon Jung, Minkyu Choi, Yoon Young Son, Taeil Kim, Hyoung-Il Cheong, Jae-Ho Hyung, Woo Jin Noh, Sung Hoon Chung, Hyunsoo Park, Jun Chul Shin, Sung Kwan Lee, Sang Kil Lee, Yong Chan Koom, Woong Sub Lim, Joon Seok Chung, Hyun Cheol Rha, Sun Young Kim, Hyunki Oncotarget Research Paper Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials. Impact Journals LLC 2016-06-16 /pmc/articles/PMC5190122/ /pubmed/27331626 http://dx.doi.org/10.18632/oncotarget.10115 Text en Copyright: © 2016 Kim et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kim, Hyo Song
Shin, Su-Jin
Beom, Seung-Hoon
Jung, Minkyu
Choi, Yoon Young
Son, Taeil
Kim, Hyoung-Il
Cheong, Jae-Ho
Hyung, Woo Jin
Noh, Sung Hoon
Chung, Hyunsoo
Park, Jun Chul
Shin, Sung Kwan
Lee, Sang Kil
Lee, Yong Chan
Koom, Woong Sub
Lim, Joon Seok
Chung, Hyun Cheol
Rha, Sun Young
Kim, Hyunki
Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title_full Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title_fullStr Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title_full_unstemmed Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title_short Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
title_sort comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190122/
https://www.ncbi.nlm.nih.gov/pubmed/27331626
http://dx.doi.org/10.18632/oncotarget.10115
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