Pulmonary adenocarcinomas with micropapillary component significantly correlate with recurrence, but can be well controlled with EGFR tyrosine kinase inhibitors in the early stages

Abstract

Pulmonary adenocarcinoma with a micropapillary component (PA-MPC) is known to exhibit biologically aggressive behavior. The aim of this study was to evaluate the clinicopathological characteristics of early-stage PA-MPC and to investigate the correlation between PA-MPC and epidermal growth factor receptor (EGFR) or KRAS mutation status. We reviewed 440 PA patients who underwent resection. We defined PA-MPC as adenocarcinoma with MPC occupying at least 5% of the entire tumor. EGFR and KRAS mutations were detected using established methods. Of the 440 cases, 256 cases were classified as stage IA, of which 53 cases (20.7%) had MPC. The 5-year disease-free survival rates in the MPC-negative and MPC-positive groups of patients with stage IA tumors were 92.1% and 77.6%, respectively. The difference in these rates was statistically significant (p = 0.003), whereas the difference in overall survival between the groups was not statistically significant (p = 0.973). The mean percentage of MPC was 20.4% in the recurrent group and 18.3% in the non-recurrent group, with no significant correlation (p = 0.996). Of the 10 recurrent cases, 6 cases exhibited EGFR mutations; the 5 cases treated with a tyrosine kinase inhibitor (TKI) achieved long survival (median, 64.6 months). No KRAS mutations were detected in any of the 10 cases. PA-MPCs were strongly associated with recurrence, but were not influenced by the MPC percentage even in early-stage lesions. Moreover, PA-MPCs with recurrence were associated with relatively better survival. These findings indicate that PA-MPCs were biologically aggressive but could be controlled with EGFR-TKIs.