Histopathological subtyping is a prognostic factor in stage IV lung adenocarcinoma.

Lung adenocarcinoma is a heterogeneous tumor made of different architectural patterns. These tumors are classified into subtypes according to the predominant pattern in the primary tumor because the predominant pattern is related to overall survival. The prognostic role of these subtypes in stage IV disease is not well known, and most lung adenocarcinomas are diagnosed at the stage of metastatic disease. We aimed to evaluate the prognostic role of histopathological subtypes in lung adenocarcinoma metastases in a retrospective study of 253 patients with clinical, histopathological and molecular data. The presence of the solid subtype was related to overall survival (p = 0.045); the median overall survival was 6.8 months (95 % confidence interval (95 %CI) 4.4-9.1) when present and 11.1 months (95 %CI 8.6-21.3) when absent. Thyroid transcription factor 1 (TTF-1) immunohistochemistry was related to overall survival (p < 0.001); the median overall survival was 11.2 months (95 %CI 8.4-17.7) when positive and 4 months (95 %CI 2.3-5.7) when negative. On multivariate analysis, the presence of the solid subtype (p = 0.0036, hazard ratio (HR) 1.55, 95 %CI 1.03-2.34), TTF-1 positivity (p = 0.044, HR 0.64, 95 %CI 0.42-0.98), age <60 years at the time of resection (p = 0.017, HR 1.89; 95 %CI 1.12-3.21), performance status <2 (p = 0.017, HR 0.57; 95 %CI 0.36-0.91), treatment by chemotherapy (p = 0.033, HR 0.54, 95 %CI 0.31-0.95), and treatment by tyrosine kinase inhibitor or immunotherapy (p = 0.013, HR 0.36, 95 %CI 0.17-0.81) were related to overall survival. The evaluation of architectural pattern in metastases in stage IV patients provides further information for physicians about patient prognosis. This information might be included in clinical trials in patients with stage IV lung adenocarcinoma.