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Original Research: LUNG CANCER |

Clinical Significance of Thyroid Transcription Factor-1 in Advanced Lung Adenocarcinoma Under Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor TreatmentThyroid Transcription Factor-1 and Adenocarcinoma

Kuei-Pin Chung, MD; Yen-Tsung Huang, MD, MPH; Yih-Leong Chang, MD, PhD; Chong-Jen Yu, MD, PhD; Chih-Hsin Yang, MD, PhD; Yeun-Chung Chang, MD; Jin-Yuan Shih, MD, PhD; Pan-Chyr Yang, MD, PhD, FCCP
Author and Funding Information

From the Department of Laboratory Medicine (Dr Chung), the Department of Pathology (Dr Y-L Chang), the Department of Internal Medicine (Drs Yu, Shih, and P-C Yang), and the Department of Medical Imaging (Dr Y-C Chang), National Taiwan University Hospital, College of Medicine, National Taiwan University; Graduate Institute of Oncology (Dr C-H Yang), Cancer Research Center, National Taiwan University, Taipei, Taiwan; and the Departments of Biostatistics and Epidemiology (Dr Huang), School of Public Health, Harvard University, Boston, MA.

Correspondence to: Jin-Yuan Shih, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S Rd, Taipei 100, Taiwan; e-mail: jyshih@ntu.edu.tw


Funding/Support: This work was supported by the National Science Council [Grants 98-2314-B-002-117-MY3 and 98-2628-B-002-087-MY3], Taiwan; and National Taiwan University [Grant 99C101-101], Taiwan.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(2):420-428. doi:10.1378/chest.10-3149
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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.

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