title: Clinical significance of thyroid transcription factor-1 in advanced lung adenocarcinoma under epidermal growth factor receptor tyrosine kinase inhibitor treatment.
abstract: BACKGROUND
  Thyroid transcription factor 1 (TTF-1) positivity correlates with a higher prevalence of epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma. It is unknown whether TTF-1 expression affects the clinical outcome of patients with advanced lung adenocarcinoma, who have received EGFR tyrosine kinase inhibitors (TKIs) during the treatment course.
  
  
  METHODS
  This study enrolled patients with advanced lung adenocarcinoma who had results of EGFR mutation analysis and TTF-1 immunostaining. The impact of TTF-1 expression on overall survival (OS) and progression-free survival (PFS) under EGFR TKI treatment was evaluated. Multivariate analyses were done to examine the independent predictors of OS and PFS.
  
  
  RESULTS
  Of 496 patients with advanced lung adenocarcinoma, 443 had TTF-1-positive adenocarcinoma. Patients with TTF-1-positive lung adenocarcinoma had longer OS than did those with TTF-1-negative lung adenocarcinoma (median survival, 27.4 vs 11.8 months, P = .001). In patients with EGFR TKI treatment, those with TTF-1-positive lung adenocarcinoma and mutant EGFR had longer OS. In patients with EGFR mutation, those with TTF-1-positive lung adenocarcinoma had longer PFS than did those with TTF-1-negative lung adenocarcinoma (median survival, 8.7 vs 5.7 months, P = .043). Multivariate analysis showed that negative TTF-1 expression is a predictor for shorter OS, and a predictor for shorter PFS under EGFR TKI treatment.
  
  
  CONCLUSIONS
  TTF-1 shows independent prognostic significance in advanced lung adenocarcinoma. Patients with TTF-1-negative lung adenocarcinoma have not only shorter OS, but also shorter PFS under EGFR TKI treatment, despite the existence of mutant EGFR. Further studies are needed to investigate the optimal treatment of patients with TTF-1-negative lung adenocarcinoma.
authors.affiliation: Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuei-Pin
authors.initials: KP
authors.lastname: Chung
authors.affiliation: Departments of Biostatistics and Epidemiology, School of Public Health, Harvard University, Boston, MA.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Graduate Institute of Oncology, Cancer Research Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Yeun-Chung
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Pathology, National Taiwan University, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan. Electronic address: jyshih@ntu.edu.tw.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.affiliation: Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012042:Registries; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D015820:Cadherins; C117307:KRAS protein, human; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D014746:Vimentin; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins