title: Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma.
abstract: BACKGROUND
  In the current study, the authors investigated whether thyroid transcription factor-1 (TTF-1) expression is correlated with the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and whether it stratifies patients with stage I lung adenocarcinoma with respect to disease recurrence.
  
  
  METHODS
  Patients with stage I lung adenocarcinoma were classified according to the IASLC/ATS/ERS classification. Tissue microarrays were constructed and immunostaining for TTF-1 was performed. A total of 452 cases were available for analysis. Tumors were dichotomized based on the intensity of nuclear TTF-1 expression as negative (score of 0) or positive (score of 1-3). The cumulative incidence of recurrence (CIR) was used to estimate disease recurrence probabilities.
  
  
  RESULTS
  TTF-1 expression was identified in 92% of patients, including 100% of patients with minimally invasive or lepidic-predominant adenocarcinoma, 94% of patients with acinar-predominant adenocarcinoma, 98% of patients with papillary-predominant adenocarcinoma, 93% of patients with micropapillary-predominant adenocarcinoma, 86% of patients with solid-predominant adenocarcinoma, 67% of patients with colloid-predominant adenocarcinoma, and 47% of patients with invasive mucinous carcinoma. The CIR for patients with negative TTF-1 expression (n = 34 patients; 5-year CIR, 40%) was significantly higher than that for patients with positive TTF-1 expression (n = 418 patients; 5-year CIR, 15%) (P < .001). Among the patients with intermediate-grade tumors, the CIR for patients with negative TTF-1 expression (n = 16 patients; 5-year CIR, 45%) was significantly higher than that for patients with positive TTF-1 expression (n = 313 patients; 5-year CIR, 14%) (P < .001). On multivariate analysis, negative TTF-1 expression was found to be significantly correlated with an increased risk of disease recurrence (hazards ratio, 2.55; P = .009).
  
  
  CONCLUSIONS
  TTF-1 expression was found to be an independent predictor of disease recurrence, stratifying intermediate-grade tumors into 2 prognostic subsets, and it correlates with the IASLC/ATS/ERS classification.
authors.affiliation: Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nitadori
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors