A comprehensive evaluation of clinicopathologic characteristics, molecular features and prognosis in lung adenocarcinoma with solid component

We have reported that solid predominant lung adenocarcinoma according to the IASLC/ATS/ERS classification was associated with poor prognosis. However, the correlation of solid component with clinicopathological, molecular features, and prognosis in all lung adenocarcinoma patients remains unexplored. Surgically resected lung adenocarcinomas were divided into three groups, solid predominant (solid component accounting for at least 50%), solid minor (solid component accounting for 5-45%) and solid negative. Patients' clinicopathological characteristics, disease free survival (DFS), overall survival (OS) and molecular alterations, including EGFR, KRAS, FGFR, etc., were analyzed. Of 1098 lung adenocarcinomas, 198 were solid predominant, 132 were solid minor, and 768 were solid negative. Solid positive patients, including solid predominant and solid minor, had significantly worse DFS (p < 0.0001) and OS (p < 0.0001) compared with solid negative group, so were solid minor patients (both p < 0.0001). Cox multivariate analysis revealed that solid positive pattern was an independent predictor for DFS [hazard ratio (HR) 1.495, 95% confidence interval (CI) 1.004-2.233; p = 0.034] and OS [HR 1.561, 95% CI 1.03-2.342; p = 0.016]. The frequency of FGFR fusions was significantly higher in solid positive lung adenocarcinomas than in solid negative group (1.5 vs. 0.3%, p = 0.048). The response rate to EGFR-tyrosine kinase inhibitors (TKIs) was 66.7% in EGFR-mutated solid positive patients after recurrence. This study represents the first comprehensive clinical investigation of solid component in lung adenocarcinomas, identifying solid positive pattern as an independent poor prognostic indicator in lung adenocarcinoma.