Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.