title: A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma.
abstract: The International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) has recently proposed a new lung adenocarcinoma classification. We investigated whether nuclear features can stratify prognostic subsets. Slides of 485 stage I lung adenocarcinoma patients were reviewed. We evaluated nuclear diameter, nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, prominence of nucleoli, intranuclear inclusions, mitotic count/10 high-power fields (HPFs) or 2.4 mm(2), and atypical mitoses. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification and grouped by architectural grade into low (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic predominant), intermediate (papillary or acinar), and high (micropapillary or solid). Log-rank tests and Cox regression models evaluated the ability of clinicopathologic factors to predict recurrence-free probability. In univariate analyses, nuclear diameter (P=0.007), nuclear atypia (P=0.006), mitotic count (P<0.001), and atypical mitoses (P<0.001) were significant predictors of recurrence. The recurrence-free probability of patients with high mitotic count (≥5/10 HPF: n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (2-4/10 HPF: n=106, 80%), and low (0-1/10 HPF: n=204, 91%, P<0.001). Combined architectural/mitotic grading system stratified patient outcomes (P<0.001): low grade (low architectural grade with any mitotic count and intermediate architectural grade with low mitotic count: n=201, 5-year recurrence-free probability=92%), intermediate grade (intermediate architectural grade with intermediate-high mitotic counts: n=206, 78%), and high grade (high architectural grade with any mitotic count: n=78, 68%). The advantage of adding mitotic count to architectural grade is in stratifying patients with intermediate architectural grade into two prognostically distinct categories (P=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (P=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs low: P=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice.
authors.affiliation: Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.forename: Kei
authors.initials: K
authors.lastname: Suzuki
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Kachala
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Andre L
authors.initials: AL
authors.lastname: Moreira
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen