A Comprehensive Investigation of Molecular Features and Prognosis of Lung Adenocarcinoma with Micropapillary Component

Introduction: Both micropapillary predominant lung adenocarcinoma according to the IASLC/ATS/ERS classification and lung adenocarcinoma with a micropapillary component have been reported to be associated with poor prognosis. However, whether they have different prognosis remains undetermined. Methods: Out of 1302 lung adenocarcinoma patients, 21 patients with micropapillary predominant lung adenocarcinoma (MPP) and 100 patients with nonmicropapillary predominant tumors harboring a micropapillary component of at least 5% (MPC) were investigated for clinicopathologic characteristics, recurrence-free survival (RFS), overall survival (OS), and spectrum of well-identified driver mutations including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET. Results: Twenty out of 21 (95.2%) micropapillary predominant lung adenocarcinoma harbored driver mutations in EGFR (85.7%), HER2 (4.8%), or RET (4.8%). MPP had significantly worse RFS than MPC in stage I patients (p = 0.003), but not in stages II-III patients. The overall survival was comparable between MPP and MPC regardless of disease stages. Objective response was achieved in 13 out of the 18 MPP or MPC patients with EGFR mutations who received EGFR tyrosine kinase inhibitors (TKIs) after disease recurrence. The postrecurrence survival was significantly better in EGFR-mutated patients who were treated with EGFR TKIs compared to those who did not receive TKIs (p = 0.003). Conclusions: Micropapillary predominant lung adenocarcinoma is a disease that could be largely defined by targetable driver mutations. For stage I lung adenocarcinoma, MPP was even more likely to recur than MPC. EGFR TKIs might help to control the recurrent disease for MPP or MPC patients harboring EGFR mutations.