The Role of Human Epidermal Growth Factor Receptor 2 as a Prognostic Factor in Lung Cancer A Meta-Analysis of Published Data

Introduction: Human epidermal growth factor receptor 2 (HER2) is regarded as a poor prognostic factor in many tumors. Conflicting data in many literatures were reported about the association between HER2 and poor prognosis in lung cancer. Methods: We conducted a meta-analysis of published studies from 1966 to the 12th week of 2010. In absence of significant quality difference between positive and negative studies, combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. Results: Forty studies(6135 patients) were included in the analysis. The pooled data showed that HER2 overexpression was a marker of poor prognosis in lung cancer. HR was 1.48 (95% CI: 1.22-1.80) and 3.11 (95% CI: 2.26-4.28) for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) by immunohistochemistry (IHC) assay, respectively. In the NSCLC subgroup analysis of early stage and ethnicities using IHC and in SCLC subgroup of extensive stage using IHC, it also showed that HER2 overexpression determined by IHC was a marker of poor prognosis in NSCLC and SCLC. In other subgroup of squamous cell carcinoma tested by IHC, the combined HR was 0.87 (95% CI: 0.61-1.25), indicating that HER2 overexpression was not a prognostic factor for squamous cell carcinoma. Finally, in the subgroup analysis of HER2 amplification status of NSCLC using fluorescence in situ hybridization, we also found that HER2 amplification determined by fluorescence in situ hybridization was not significantly related to prognosis. Conclusions: Although bias could be inevitable, this meta-analysis suggests that HER2 overexpression is a poor prognostic factor in lung cancer, especially for SCLC, adenocarcinoma, and early-stage NSCLC.