HER2 mutations in pulmonary adenocarcinoma presenting with ground-glass nodules

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Abstract
Human epidermal growth factor receptor 2 (HER2) mutations have been identified as oncogenic drivers and therapeutic targets in Non-small cell lung cancers (NSCLCs). The role of HER2 mutation in lung adenocarcinoma presented as sub-solid nodules (SSNs) have not been distinctly defined. This study comprehensively investigated the clinicopathological characteristics of HER2 mutation in patients with pulmonary SSNs. In total, 717 patients with completely resected NSCLCs presented as SSNs were examined for HER2 mutation from January 2016 to December 2018. Age, sex, smoking history, radiologic features, operative procedure, pleural invasion, histologic subtypes and tumor-node-metastasis stage were collected. Kaplan-Meier method was used to estimate DFS, Log-rank test was used to compare the survival data. Logistic regression model was used to identify the predictors for HER2 mutation and the predictive nomogram was built. In this study, 47(6.6%) SSNs carried HER2 mutations. HER2 mutations were more frequent in subjects with younger age (P < 0.001) and smaller tumor size (P < 0.001), and were prone to occur in AIS and MIA (P < 0.001). The 5- year DFS rates for HER2 mutation and HER2 wild-type groups were similar (P = 0.509). According to the logistic regression analysis, age and maximum tumor size were independent variables correlated with HER2 mutation. A predictive nomogram model was constructed with a concordance statistic of 0.79 (0.71–0.87). HER2 mutation was not uncommon in pulmonary SSNs. Younger age and smaller tumor size were associated with increased odds of HER2 mutation.

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