Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

Abstract

The ToGA trial demonstrated the beneficial effect of trastuzumab in gastric cancer patients with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors. Therefore, evaluation of the relationship between HER2 expression and gastric cancer biology using a validated system has become an even more important task. Herein, we verified the correlation between HER2 overexpression in the tumor and the clinical course of gastric cancer patients. A total of 1,006 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using the tissue microarrays approach. HER2 expression was determined based on an immunohistochemistry score of 3+, or an immunohistochemistry score of 2+ plus HER2 gene amplification as detected by double-color fluorescent in situ hybridization. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Then, in 948 patients who had undergone curative resection, HER2 status was compared with the survival. HER2 overexpression was detected in 118 (11.7 %) patients. HER2 overexpression was correlated with age, gender, grade of differentiation, expanding growth pattern, and nodal status. In the survival analysis, HER2 overexpression was not found to be correlated with either disease-specific survival or recurrence-free survival. HER2 overexpression in the tumor was not identified as a significant prognostic factor in patients with operable gastric cancer. The HER2-targeted therapy may be beneficial in a proportion of cases.