Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer

Abstract

Amplification and overexpression of human epidermal growth factor receptor-2 (HER-2) has been shown in subgroups of gastric cancer, correlated to more aggressive disease and predictive for the treatment with HER-2 antibodies. In this study, we examined the prognostic value of HER-2 expression in primary gastric cancer and in associated lymph node metastases and confirmed the role of HER-2 in tumor angiogenesis by examining vascular endothelial growth factor (VEGF) expression. Immunohistochemistry was used to detect HER-2 and VEGF expression in 110 gastric cancer specimens and associated lymph node metastases and in 96 specimens of normal gastric mucosa. The expression level of HER-2 in gastric tissues was significantly higher than in normal tissues (19.1 % vs. 8.3 %; P < 0.05). HER-2 overexpression was homogeneous in primary gastric cancer and metastatic lymph nodes (P = 0.607). There was a significant positive correlation of HER-2 expression and VEGF expression (P = 0.007). HER-2 overexpression in primary tumor correlated with lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Cox regression multivariate analyses confirmed that tumor size, histological grade, lymph node ratio, AJCC stage, chemotherapy, and HER-2 expression were all prognostic factors. Patients with HER-2 positivity in both primary and metastatic tissues (+/+) had the poorest survival (OS, 12.5 months; DFS, 11.0 months) (P < 0.01). HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.