Kuei-Pin Chung1, Yen-Tsung Huang2, Yih-Leong Chang3, Chong-Jen Yu4, Chih-Hsin Yang5, Yeun-Chung Chang4, Jin-Yuan Shih6, Pan-Chyr Yang3. 1. Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan. 2. Departments of Biostatistics and Epidemiology, School of Public Health, Harvard University, Boston, MA. 3. Department of Internal Medicine, National Taiwan University, Taipei, Taiwan. 4. Department of Medical Imaging, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taiwan. 5. Graduate Institute of Oncology, Cancer Research Center, National Taiwan University, Taipei, Taiwan. 6. 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.
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.
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: Kyuichi Kadota; Jun-Ichi Nitadori; Inderpal S Sarkaria; Camelia S Sima; Xiaoyu Jia; Akihiko Yoshizawa; Valerie W Rusch; William D Travis; Prasad S Adusumilli Journal: Cancer Date: 2012-10-23 Impact factor: 6.860