Simultaneous detection of expression and gene mutations of HER2/neu in chinese patients with gastric cancer

Abstract

HER2/neu is one of the few identified oncogenes in tumorigenesis. Attention has been focused on the potential effect of HER2/neu mutations in the tyrosine kinase domain on carcinoma-targeted therapy. However, data concerning HER2/neu mutations in Chinese patients with gastric cancer (GC) are limited. This study aimed to detect the expression and somatic mutations of HER2/neu in Chinese patients with GC. Immunohistochemical staining for HER2/neu was performed on 72 formalin-fixed, paraffin-embedded specimens of GC (40 intestinal and 32 diffuse type). The correlation between the overexpression of HER2/neu and clinicopathological parameters was statistically analyzed. Somatic mutations in the tyrosine kinase domain of HER2/neu in the 72 patients were detected by direct sequencing. In the GC group, overexpression of HER2/neu was detected in 13 of the 72 GC patients and in 4 of the 72 adjacent tissues in the non-tumorous group (18.1 vs. 5.6%, P<0.05). Furthermore, the intestinal type of GC exhibited a higher rate of HER2/neu overexpression than the diffuse type (29.7 vs. 5.7%, P<0.05). The rate of HER2/neu overexpression in stage III-IV (TNM stage) GC cases was significantly higher than that in stage I-II (28.2 vs. 6.6%, P<0.05). HER2/neu overexpression correlated with a significantly less favorable patient survival (P=0.046). No somatic mutations in the tyrosine kinase domain of HER2/neu were detected in tumor tissues or the corresponding non-tumorous ones in the specimens obtained from the 72 Chinese GC patients. Results suggest that overexpression of HER2/neu is a frequent molecular event strongly associated with a poor patient prognosis, whereas the incidence of somatic mutations of the HER2/neu kinase domain is more likely a low-frequency event in Chinese GC patients.