Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer

Abstract

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.

Keywords: Beta Catenin; Epstein-Barr Virus Infections; Human epidermal growth factor receptor-2; Stomach Neoplasms; Tumor Suppressor Protein p53.

FIG. 1. Kaplan-Meier survival curves for disease-free survival (A) and overall survival (B) according to p53 status.

FIG. 2. Kaplan-Meier survival curves for disease-free survival (A) and overall survival (B) according to beta-catenin status.