Correlation of survival and EGFR mutation with predominant histologic subtype according to the new lung adenocarcinoma classification in stage IB patients

Background: A new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) has recently been published. This study aimed to investigate the utility of the new histological classification for identifying the prognostic subtypes of adenocarcinomas in stage IB patients. Correlations between the classification and the presence of epidermal growth factor receptor (EGFR) mutation status was also studied. Methods: One hundred and thirty-six patients with stage IB lung adenocarcinoma operated on in Zhejiang Cancer Hospital were identified between 2002 and 2011. Patients overall survival and disease-free survival were calculated using Kaplan-Meier and Cox regression analyses. EGFR mutations were detected using the amplification refractory mutation system. Results: A total of 136 cases were included in current study, of which 38 were papillary predominant, 39 were acinar predominant, 22 were micropapillary predominant, 21 were lepidic predominant subtypes, 14 were solid predominant, and 2 were variants of invasive adenocarcinoma. Patients with micropapillary- and solid-predominant tumors had the lowest five-year disease-free survival (28.4 and 36.7%, respectively). Univariate and multivariate analysis showed that the micropapillary-predominant subtype was an independent predictor of disease-free survival (P = 0.0041 and 0.048, respectively), but not overall survival (P = 0.175 and 0.214, respectively). EGFR mutations were significantly associated with the micropapillary-predominant subtype patients (P = 0.0026). The EGFR mutation frequency is lower in the solid-predominant subtype than other subtypes (P = 0.0508). Conclusions: The predominant subtype in the primary tumor was associated with prognosis in resected stage IB lung adenocarcinoma. The EGFR mutation frequency of micropapillary-predominant subtype is higher than other subtypes.