Driver mutation profiles and clinicopathological correlation in pulmonary adenocarcinoma with a micropapillary component

Abstract

Pulmonary adenocarcinoma (PA) with a micropapillary component (PA-MPC) is considered a highly aggressive neoplasm. The molecular profile of PA-MPC has not yet been clearly elucidated. Based on these, we performed next-generation sequencing and quantitative real-time polymerase chain reaction (qPCR) to detect the driver mutation profiles of 50 PA-MPC cases and confirmed the results by Sanger sequencing. In addition, in 10 selected MPC-predominant cases, we captured the MPC and non-MPC by laser-capture microdissection and sequenced them separately to investigate the differences in driver mutation profiles between MPC and non-MPC. In 50 PA-MPC cases, the prevalence rates of EGFR, KRAS, and PIK3CA somatic mutations were 76.0%, 6.0%, and 2.0%, respectively; no BRAF, NRAS, ALK, PDGFRA, or other mutations were found. With regard to the MPC, EGFR mutation was more frequent in MPC-predominant cases (18/20; 90%) than in non-MPC-predominant cases (20/30; 66.7%). The overall survival of the MPC-predominant group was significantly worse than that of the non-MPC-predominant group. In the 10 microdissected MPC-predominant cases, the EGFR mutation was identical in both components and was consistent with previous results without microdissection. In conclusion, our study indicated that EGFR mutations were frequent in PA-MPC. Paired MPC and non-MPC from the same cases had the same driver mutation profiles.