Clinical significance of p53 protein, beta-catenin, and HER2 in patients with Epstein-Barr virus-associated gastric cancer.

Abstract

22 Background: Epstein-Barr virus (EBV) infection can cause cancer tumorigenesis and malignant transformation of host cells through the activation of oncogenic pathways. Therefore, we assessed the expression of p53 protein, beta-catenin, and HER2 and their prognostic implication in patients with EBV-associated gastric cancer (EBVaGC). Methods: 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 results of immunohistochemistry were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result; strong positive cytoplasmic-nuclear expression patterns for β-catenin ( ≥ 10%) were considered altered expression; moderate or strong complete or basolateral membrane staining in 10% of tumor cells for HER2 was reported as a positive results. Results: The median age of the patients was 62 years (32-80) and 93 (79.5%) were male. The pathologic stages were as follows : stage I (n = 74), stage II (n = 25), and stage III (n = 18). Among the 117 patients, immunohistochemical staining for p53 was performed in 105 patients and 25 patients (23.8%) were positive. Beta-catenin was positive in 10 patients (17.5%) and HER2 was positive in 8 patients (6.8%), respectively. The positive expression of p53 was significantly associated with a high T stage (p = 0.006). Conversely, more patients without lymph node metastasis were p53 positive (p = 0.013). In the univariate analysis, the patients with p53 positive tumors showed a significantly improved disease-free survival (DFS) compared to the patient with negative tumors (p = 0.022), although the p53 status was marginally associated with overall survival (OS)(p = 0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Meanwhile, beta-catenin and HER2 was not found to be associated with DFS and OS in the survival analysis. Conclusions: The current study found a significant correlation between p53 expression and tumor progression in patients with EBVaGC.