PMID- 31594682
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 215
IP  - 11
DP  - 2019 Nov
TI  - Differential expression of HER2 and downstream proteins in prediction of advanced 
      tumor phenotypes and overall survival of patients with Epstein-Barr 
      virus-positive vs. negative gastric cancers.
PG  - 152675
LID - S0344-0338(19)31206-3 [pii]
LID - 10.1016/j.prp.2019.152675 [doi]
AB  - This study evaluated the associations of HER2 protein, HER2 gene amplification, 
      and positivity for p-AKT, p-ERK, and p-PLCgamma proteins with clinicopathological 
      status and overall survival (OS) of patients who had Epstein-Barr 
      virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; 
      n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence 
      in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and 
      amplified HER2 gene. p-AKT (p =  0.035) and p-ERK (p =  0.001) were inhibited in 
      EBVaGC than in EBVnGC, while p-PLCgamma (p =  0.034) was upregulated. Among EBVaGC 
      patients, p-ERK positivity was associated with Lauren classification (p = 0.023), 
      and p-PLCgamma positivity was inversely associated with TNM stage (p = 0.041) and 
      lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 
      expression was associated with distant metastasis (p = 0.043) and p-AKT 
      positivity was associated with intestinal subtype (p < 0.004), lymph node 
      metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, 
      p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than 
      EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) 
      was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT 
      positivity (p = 0.010), and p-PLCgamma (p <  0.001) were associated with worse OS in 
      EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 
      1.559 to 4.028, p <  0.001), HER2 high expression (95% CI: 1.058 to 2.454, p =  
      0.026), and p-PLCgamma positivity (95% CI: 1.056 to 2.435, p = 0.027) were 
      independent prognostic predictors of OS in EBVnGC patients. Our results indicated 
      that p-AKT positive patients presented worse OS than p-AKT negative ones in 
      EBVaGC, as well as, HER2, p-AKT, and p-PLCgamma are prognostic biomarkers for OS in 
      EBVnGC patients.
CI  - Copyright (c) 2019 Elsevier GmbH. All rights reserved.
FAU - Zhang, Yi-Wang
AU  - Zhang YW
AD  - Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
FAU - He, Dan
AU  - He D
AD  - Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
FAU - Tan, Cui
AU  - Tan C
AD  - Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 
      No. 107 Yangtze River Road, Guangzhou 510120, Guangdong Province, China.
FAU - Dong, Min
AU  - Dong M
AD  - Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
FAU - Zhou, Lu
AU  - Zhou L
AD  - Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
FAU - Shao, Chun-Kui
AU  - Shao CK
AD  - Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic 
      address: chunkuishao2011@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190927
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Adenocarcinoma/*metabolism/mortality/*virology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/analysis
MH  - Epstein-Barr Virus Infections/complications
MH  - Female
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Phospholipase C gamma/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, ErbB-2/*biosynthesis
MH  - Stomach Neoplasms/*metabolism/mortality/*virology
OTO - NOTNLM
OT  - Biomarker
OT  - Epstein-Barr virus
OT  - Gastric cancer
OT  - HER2
OT  - Prognosis
EDAT- 2019/10/09 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/10/10 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/09/17 00:00 [revised]
PHST- 2019/09/27 00:00 [accepted]
PHST- 2019/10/09 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/10/10 06:00 [entrez]
AID - S0344-0338(19)31206-3 [pii]
AID - 10.1016/j.prp.2019.152675 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2019 Nov;215(11):152675. doi: 10.1016/j.prp.2019.152675. Epub 
      2019 Sep 27.