Bin Pan, Rui Wang, Yangle Huang, David Garfield, Jie Zhang, Haiquan Chen

Although over-expression of hepatocyte growth factor (HGF) and neuregulin-1 (NRG1) are important mechanisms involved in acquired drug-resistance in many cancers, few reports have evaluated their clinicopathologic features and prognostic significance. The aim of our study was to investigate protein expressions of HGF and NRG1 in lung adenocarcinomas and their association with clinicopathologic parameters, oncogenic mutations, and the prognosis. HGF and NRG1 protein tumor/stroma expressions were evaluated by immunohistochemistry (IHC) in 115 surgically resected lung adenocarcinomas and were correlated with clinicopathologic and molecular variables including tumor size, tumor node metastasis stage, differentiation, oncogenic mutations (EGFR, KRAS, HER2, BRAF) and ALK fusions, relapse-free survival, and overall survival. Positive IHC HGF tumor and stroma staining were found in 49 (42.61%) and 12 (10.43%) cases, respectively, while positive IHC NRG1 tumor and stroma staining were found in 56 (48.70%) and eleven (9.57%) cases, respectively. Dual positive IHC HGF and NRG1 tumor staining was 12.17%. EML4-ALK fusion more significantly existed in HGF-tumor positive samples (P=0.03), positive NRG1 protein stroma expression was significantly associated with male sex (P=0.04), while HGF and NRG1 dual tumor-positive mainly existed in the tumor size >3 cm group (P=0.0231). No significant clinically prognostic difference was found between patients with HGF/NRG1-positive expression and those with HGF/NRG1-negative expression. This study represents the first comprehensive analysis of HGF and NRG1 tumor and stroma expressions in patients with surgically resected lung adenocarcinomas. Our molecular data, in conjunction with clinical and pathological features, as well as their effects on survival indicated to us that patients with HGF- and NRG1-negative expression tended to have better survival, but these results probably did not warrant these markers to be indicators of poor prognosis.