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Background    Human epidermal growth factor receptor  ( HER ) -2  is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of  HER-2  within the wild-type  epidermal growth factor receptor  ( EGFR ) lung adenocarcinoma population in China.    Methods  Formalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for  HER-2  mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry. All samples positive for  HER-2  mutation underwent direct sequencing for further verification.    Results    HER-2  mutation was detected in 22/456 cases (4.8 %); the rate was 6.7 % among 331 triple-negative samples (i.e., wild-type EGFR, anaplastic lymphoma kinase, and ROS proto-oncogene 1). Direct sequencing confirmed that the results were consistent with those obtained by ARMS analysis in 19 cases. The positive rate was 15.4 % by immunohistochemical analysis of HER-2 expression; this was not correlated with mutation rate.  HER-2  mutation and positivity were not correlated with gender, age, smoking status, disease stage, or histological subtype. The 22 cases of  HER-2  mutations occurred only in acinar (36.4 %), papillary (36.4 %), minimally invasive (13.6 %), solid (9.2 %), and invasive mucinous (4.5 %) subtypes. Disease-free and overall survival were not associated with  HER-2  mutation or HER-2 protein overexpression.    Conclusion  The  HER-2  mutation rate was 4.8 % among  EGFR  wild-type lung adenocarcinoma patients in China, and 6.7 % among driver genes, triple-negative lung adenocarcinoma. The incidence of  HER-2  mutation varied among different lung adenocarcinoma subtypes, occurring mainly in acinar and papillary predominant subtypes. 15.4 % of  EGFR  wild-type lung adenocarcinoma patients showed HER-2 protein overexpression, but this was not correlated to  HER-2  mutation. Existing follow-up data did not show a correlation between  HER-2  mutation with DFS or OS.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-016-2875-z) contains supplementary material, which is available to authorized users.

Epidemiological study of HER-2 mutations among EGFR wild-type lung adenocarcinoma patients in China