Cribriform Subtype is an Independent Predictor of Recurrence and Survival After Adjustment for the Eighth Edition of TNM Staging System in Patients With Resected Lung Adenocarcinoma

Abstract

Introduction: At present, cribriform arrangements are regarded as a pattern of acinar adenocarcinoma. However, recent studies have indicated that clinical outcomes for lung adenocarcinoma patients with cribriform subtype are unfavorable. To validate the prognostic significance of the cribriform pattern, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the eighth edition of the TNM staging system.

Methods: Tumors were classified in accordance with the 2015 WHO classification of lung carcinomas. The cribriform pattern was defined by invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests of tumors cells that produce glandular lumina. Recurrence-free probability (RFP) and overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model.

Results: After the addition of the cribriform pattern, 54 of 90 acinar-predominant tumors were reclassified as cribriform subtype. Five-year RFP for patients with the cribriform subtype (51%) was lower than it was for patients with acinar and papillary subtype (81% and 80%, respectively) but was comparable to that for patients with solid subtype (48%). Five-year OS for patients with the cribriform subtype (49%) was lower than it was for patients with acinar and papillary subtype (90% and 81%, respectively). On multivariate analysis adjusted for the eighth edition of the TNM staging system, the cribriform subtype was an independent prognostic factor of a worse RFP and OS.

Conclusions: We have validated that the cribriform subtype is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.

Keywords: Adenocarcinoma; Cribriform pattern; Histologic subtype; Lung; Prognosis.