Originally published as JCO Early Release 10.1200/JCO.2008.17.0043 on December 8 2008

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Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma

Valsamo K. Anagnostou, Konstantinos N. Syrigos, Gerold Bepler, Robert J. Homer, David L. Rimm

From the Department of Pathology, Yale University School of Medicine, New Haven, CT; Oncology Unit, 3rd Department of Medicine, School of Medicine, University of Athens, Sotiria General Hospital, Athens, Greece; and the Division of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL

Corresponding author: David L. Rimm, MD, PhD, Department of Pathology, BML 116, Yale University School of Medicine, 310 Cedar St, PO Box 208023, New Haven, CT 06520-8023; e-mail: david.rimm{at}yale.edu

Purpose Thyroid transcription factor 1 (TTF1) is a transcription factor that regulates the expression of multiple genes involved in lung development. It is preferentially expressed in adenocarcinomas of the lung and has been investigated as a potential prognostic parameter in patients with lung cancer, with conflicting results. We quantitatively assessed TTF1 protein expression in two large and independent data sets to investigate the impact of TTF1 nuclear expression on patient survival.

Patients and Methods Automated quantitative analysis, a fluorescent-based method for analysis of in situ protein expression, was used to assess a series of cell lines to find the threshold of detection of TTF1 expression. Then two independent cohorts (176 and 237 cases, respectively) were measured by the same technique, and TTF1 expression was correlated with survival.

Results Tumors expressed TTF1 in 45% and 58% of the cases in each cohort. TTF1 was consistently expressed in adenocarcinomas (n = 61 and 73; Spearman = 0.313 and 0.4 for the first and second set, respectively; P < .0001) independent of their differentiation and stage. Survival analysis showed that patients with stage I adenocarcinoma with TTF1 expression had a longer median overall survival than those without expression (n = 43, 44.3 v 26.2 months, P = .05 for the first cohort; n = 87; 49.7 v 38.5 months, P = .03 for the second cohort) Multivariate analysis revealed an independent lower risk of death for patients with stage I adenocarcinoma with TTF1-expressing tumors (hazard ratio = 0.479, 95% CI, 0.235 to 0.977; P = .043).

Conclusion TTF1 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of patients with stage I lung adenocarcinoma.

published online ahead of print at www.jco.org on December 8, 2008.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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