title: The cribriform pattern identifies a subset of acinar predominant tumors with poor prognosis in patients with stage I lung adenocarcinoma: a conceptual proposal to classify cribriform predominant tumors as a distinct histologic subtype.
abstract: The 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) lung adenocarcinoma classification emphasizes the prognostic significance of histologic subtypes. However, one limitation of this classification is that the highest percentage of patients (∼40%) is classified as acinar predominant tumors, and these patients display a spectrum of favorable and unfavorable clinical behaviors. We investigated whether the cribriform pattern can further stratify prognosis by histologic subtype. Tumor slides from 1038 patients with stage I lung adenocarcinoma (1995-2009) were reviewed. Tumors were classified according to the IASLC/ATS/ERS classification. The percentage of cribriform pattern was recorded, and the cribriform predominant subtype was considered as a subtype for analysis. The log-rank test was used to analyze the association between histologic variables and recurrence-free probability. The 5-year recurrence-free probability for patients with cribriform predominant tumors (n=46) was 70%. The recurrence-free probability for patients with cribriform predominant tumors was significantly lower than that for patients with acinar (5-year recurrence-free probability, 87%; P=0.002) or papillary predominant tumors (83%; P=0.020) but was comparable to that for patients with micropapillary (P=0.34) or solid predominant tumors (P=0.56). The recurrence-free probability for patients with ≥10% cribriform pattern tumors (n=214) was significantly lower (5-year recurrence-free probability, 73%) than that for patients with <10% cribriform pattern tumors (n=824; 84%; P<0.001). In multivariate analysis, patients with acinar predominant tumors with ≥10% cribriform pattern remained at significantly increased risk of recurrence compared with those with <10% cribriform pattern (P=0.042). Cribriform predominant tumors should be considered a distinct subtype with a high risk of recurrence, and presence (≥10%) of the cribriform pattern is an independent predictor of recurrence, identifying a poor prognostic subset of acinar predominant tumors. Our findings highlight the important prognostic value of comprehensive histologic subtyping and recording the percentage of each histologic pattern, according to the IASLC/ATS/ERS classification with the addition of the cribriform subtype.
authors.affiliation: 1] Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [3] Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Yeh
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.affiliation: Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Andre L
authors.initials: AL
authors.lastname: Moreira
authors.affiliation: 1] Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult