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

•HER2 gene amplification is more common in patients with EBVnGC than EBVaGC.•HER2 preferentially activates the AKT and PLC pathways over the MAPK pathway in EBVnGC.•In EBVaGC, p-AKT positive patients presented worse OS. As well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC p...

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Published in:Pathology, research and practice research and practice, 2019-11, Vol.215 (11), p.152675-152675, Article 152675
Main Authors: Zhang, Yi-wang, He, Dan, Tan, Cui, Dong, Min, Zhou, Lu, Shao, Chun-kui
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
Adenocarcinoma - mortality
Adenocarcinoma - virology
Adult
Aged
Aged, 80 and over
Biomarker
Biomarkers, Tumor - analysis
Epstein-Barr virus
Epstein-Barr Virus Infections - complications
Female
Gastric cancer
HER2
Herpesvirus 4, Human
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Phenotype
Phospholipase C gamma - metabolism
Prognosis
Proto-Oncogene Proteins c-akt - metabolism
Receptor, ErbB-2 - biosynthesis
Stomach Neoplasms - metabolism
Stomach Neoplasms - mortality
Stomach Neoplasms - virology
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Summary:•HER2 gene amplification is more common in patients with EBVnGC than EBVaGC.•HER2 preferentially activates the AKT and PLC pathways over the MAPK pathway in EBVnGC.•In EBVaGC, p-AKT positive patients presented worse OS. As well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients. This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ 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-PLCγ (p =  0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ 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 
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2019.152675