Prognostic Impact and Clinicopathological Correlations of the Cribriform Pattern in Pulmonary Adenocarcinoma

BackgroundA novel classification of pulmonary adenocarcinoma (ADC) distinguishing five growth patterns has been established by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. There is evidence that an additional cribriform pattern associates with a distinct clinical behavior.MethodsWe evaluated the predominant growth pattern of 674 resected ADC as recommended by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society, including the cribriform pattern. The predominant pattern type was correlated with clinical, molecular, and survival data.ResultsTwo hundred forty-eight (36.8%) of the pulmonary ADC were solid, 207 (30.6%) were acinar, 101 (15%) were papillary, 55 (8.2%) were micropapillary, 35 (5.2%) were lepidic, and 28 cases (4.2%) were cribriform predominant (cpADC). Minor cribriform components were frequently observed (28.6% of all cases). cpADC showed the second highest proliferative capacity of all patterns, no somatic mutations in the epidermal growth factor receptor (p = 0.001) and a high rate of KRAS mutations. Overall survival (OS) of patients with cpADC (mean OS: 62.7 months) ranged in between survival times of patients with acinar (mean OS: 71.3 months) and solid predominant ADC (mean OS: 54.5 months); cpADC was associated with the worst disease-free survival (DFS) of all patterns (mean DFS: 36.9 months). Both associations were confirmed by multivariate analysis (p < 0.01 for both OS and DFS). Hazard ratios for cpADC were 1.72 for OS and 2.99 for DFS, with lepidic predominant ADC set as reference (hazard ratio: 1).ConclusionsOur data support the introduction of cpADC as a novel category into future morphology based on pulmonary ADC classifications. Further international studies are required to validate the reported clinicopathological associations of the cribriform pattern.