An independent survival prognostic role for human epidermal growth factor receptor 2 in gastric cancer: evidence from a meta-analysis

Some studies have suggested that human epidermal growth factor receptor 2 (HER2) positive is associated with poor outcomes in gastric cancer (GC), whereas another inconsistent studies make the situation confused. This meta-analysis was performed to determine whether HER2 played an independent prognostic role in clinicopathological characteristics and survival outcomes of GC. Combination of GC and human epidermal growth factor 2 or HER2 or HER2/neu or erbB-2 or cerbB-2 or c-erbB2 or CD340 or p185 were used as key words. Data were compared according to the HER2 status. Time-to-event outcomes of overall survival (OS) were analyzed using Hazard Ratios (HRs) with fixed effect, while 5-year survival rate and clinicopathological factors were performed using odd ratios (OR) with random effect. Nighteen trials, from 1986 to October 2013, were identified by two independent authors. A total of 6344 GC patients were included in this meta-analysis, with 1148 HER2 protein overexpression or gene amplification. Comparison of 5-year survival of patients with HER2-positive status versus HER2-negative status showed that OR was 0.58 [95% confidence interval (CI), 0.37-0.91], and the result was significant (P = 0.02). The survival outcome of HER2 protein overexpression or gene amplification patients was worse than those with normal HER2 (HR 1.15; 95% CI 1.12-1.18; P < 0.00001). However, the difference of III-IV stage ratio between HER2-positive and HER2-negative patients was not significant (OR 1.44; 95% CI 0.95-2.18; P = 0.09) even in the subgroup analysis of Asia (P = 0.12 and Europe (P = 0.51). HER2 protein overexpression or gene amplification in GC patients is associated with a poor survival outcome, and may play a role in GC tumorigenesis.