title: Prognostic impact and clinicopathological correlations of the cribriform pattern in pulmonary adenocarcinoma.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Two 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).
  
  
  CONCLUSIONS
  Our 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.
authors: *Institute for Pathology, Heidelberg University, Heidelberg, Germany; †Translational Lung Research Centre Heidelberg (TLRC-H), Member of the German Centre for Lung Research (DZL), Heidelberg, Germany; ‡Translational Research Unit, Thoraxklinik at Heidelberg University, Heidelberg, Germany; §Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, Heidelberg, Germany; and ‖National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors: Arne
authors: A
authors: Warth
authors: Thomas
authors: T
authors: Muley
authors: Claudia
authors: C
authors: Kossakowski
authors: Albrecht
authors: A
authors: Stenzinger
authors: Peter
authors: P
authors: Schirmacher
authors: Hendrik
authors: H
authors: Dienemann
authors: Wilko
authors: W
authors: Weichert
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011013:Pneumonectomy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends