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

Hyo Song Kim, Su Jin Shin, Seung Hoon Beom, Minkyu Jung, Yoon Young Choi, Taeil Son, Hyoung Il Kim, Jae Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyunsoo Chung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sun Young Rha, Hyunki Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)44608-44620
Number of pages13
JournalOncotarget
Volume7
Issue number28
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Stomach Neoplasms
Immunohistochemistry
Human Herpesvirus 4
DNA Mismatch Repair
Therapeutics
PTEN Phosphohydrolase
Receptor Protein-Tyrosine Kinases
In Situ Hybridization
Cause of Death
Neoplasms
Clinical Trials
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

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. In: Oncotarget. 2016 ; Vol. 7, No. 28. pp. 44608-44620.
@article{539ea872e2e9453dbe7141d981f51040,
title = "Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: Implications for individualized therapy",
abstract = "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.",
author = "Kim, {Hyo Song} and Shin, {Su Jin} and Beom, {Seung Hoon} and Minkyu Jung and Choi, {Yoon Young} and Taeil Son and Kim, {Hyoung Il} and Cheong, {Jae Ho} and Hyung, {Woo Jin} and Noh, {Sung Hoon} and Hyunsoo Chung and Park, {Jun Chul} and Shin, {Sung Kwan} and Lee, {Sang Kil} and Lee, {Yong Chan} and Koom, {Woong Sub} and Lim, {Joon Seok} and Chung, {Hyun Cheol} and Rha, {Sun Young} and Hyunki Kim",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.10115",
language = "English",
volume = "7",
pages = "44608--44620",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "28",

}

Kim, HS, Shin, SJ, Beom, SH, Jung, M, Choi, YY, Son, T, Kim, HI, Cheong, JH, Hyung, WJ, Noh, SH, Chung, H, Park, JC, Shin, SK, Lee, SK, Lee, YC, Koom, WS, Lim, JS, Chung, HC, Rha, SY & Kim, H 2016, 'Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: Implications for individualized therapy', Oncotarget, vol. 7, no. 28, pp. 44608-44620. https://doi.org/10.18632/oncotarget.10115

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.

In: Oncotarget, Vol. 7, No. 28, 01.01.2016, p. 44608-44620.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry

T2 - Implications for individualized therapy

AU - Kim, Hyo Song

AU - Shin, Su Jin

AU - Beom, Seung Hoon

AU - Jung, Minkyu

AU - Choi, Yoon Young

AU - Son, Taeil

AU - Kim, Hyoung Il

AU - Cheong, Jae Ho

AU - Hyung, Woo Jin

AU - Noh, Sung Hoon

AU - Chung, Hyunsoo

AU - Park, Jun Chul

AU - Shin, Sung Kwan

AU - Lee, Sang Kil

AU - Lee, Yong Chan

AU - Koom, Woong Sub

AU - Lim, Joon Seok

AU - Chung, Hyun Cheol

AU - Rha, Sun Young

AU - Kim, Hyunki

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84978722283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978722283&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.10115

DO - 10.18632/oncotarget.10115

M3 - Article

C2 - 27331626

AN - SCOPUS:84978722283

VL - 7

SP - 44608

EP - 44620

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 28

ER -