Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance

Abstract

Purpose: Growth factor receptor-bound 2 (Grb2)-mediated HER2 signaling is thought to play a critical role in gastric cancer development, progression and metastasis. However, little is known about their expression in gastric cancer. In this study, we try to explore their relationship with clinicopathological parameters and prognostic significance in gastric cancer patients.

Materials and methods: We examined the expression of Grb2 and HER2 in normal gastric mucosa, primary gastric cancers, and lymph node metastases using immunohistochemical analysis of tissue microarrays containing specimens obtained from 1,143 patients with gastric cancer.

Results: Grb2 was overexpressed in 48% (553/1,143) of primary tumors and 59% (155/262) of lymph node metastases. We observed significant differences in Grb2 expression between the primary tumors and the lymph node metastases (P < 0.01). Also, HER2 was overexpressed in 28% (321/1,143) of the primary tumors and 30% (79/262) of the lymph node metastases. Overexpression of Grb2 and Her2 was associated with age (>60 years), tumor location (cardia of stomach), adenocarcinoma, and high/moderate differentiation. A significant relationship was found between Grb2 and HER2 expression using Chi-Square Tests and Spearman Correlation. Overexpression of Grb2 correlated significantly with poor survival rates in both univariate and multivariate analysis.

Conclusions: Our data demonstrated a progressive amplification of Grb2 and HER2 expression in gastric carcinogenesis, suggesting the importance of Grb2 and HER2 as positive biomarkers for gastric cancer development and progression.

Fig. 1

Expression of Grb2 and HER2 in gastric cancers by immunohistochemistry and Western blot. a Grb2 in primary tumor; b Grb2 in nodal metastases; c HER2 in primary tumor; d HER2 in nodal metastases; e Western blot analysis of four paired gastric cancer (C) and normal gastric mucosa specimens (N); ×200

Fig. 2

Kaplan–Meier survival curves (a) and strata analysis according to TNM (b) for Grb2