Thyroid Transcription Factor-1 Amplification and Expressions in Lung Adenocarcinoma Tissues and Pleural Effusions Predict Patient Survival and Prognosis

Abstract

Thyroid transcription factor-1 (TTF1) plays a role in lung adenocarcinoma development. We investigated the significance of TTF1 in primary lung adenocarcinomas, lymph node metastases, and malignant pleural effusions (MPEs). We studied TTF1 in 175 primary lung adenocarcinomas, 52 lymph node metastases, and 46 MPE using microarray-based fluorescence in situ hybridization, immunohistochemistry, and messenger RNA (mRNA) in situ hybridization. Real-time reverse transcription polymerase chain reaction was used to investigate correlations between TTF1 amplification and mRNA expression. Correlations between clinicopathologic characteristics, TTF1 amplification, TTF1 expressions, overall survival, and prognosis were analyzed. TTF1 was amplified in 7% of primary lung adenocarcinomas, 4% of lymph node metastases, and 4% of MPE. TTF1 amplification in lung adenocarcinomas was associated with pathologic subtypes (p = 0.029). Patients with positive TTF1 protein and mRNA expressions had improved overall survival if TTF1 was unamplified compared with those with TTF1 amplification (p = 0.068). A multivariate model did not show patients with positive TTF1 expressions tended to have better prognoses if TTF1 was unamplified compared with those with TTF1 amplification (p = 0.068). Survival time was longer for patients with TTF1 expressions in both primary lung tissues (p < 0.001) and MPE (p = 0.045). A multivariate model confirmed the prognostic value of TTF1 expressions in lung adenocarcinoma (p < 0.001). A multivariate model confirmed the prognostic value of TTF1 expressions in lung adenocarcinoma tissues (p < 0.001) while not in MPE (p = 0.058). TTF1 mRNA level was higher in cases with TTF1 amplification compared with those without TTF1 amplification. Patients with lung adenocarcinoma without TTF1 amplification tend to have better prognoses than those with TTF1 amplification in cases with positive TTF1 expressions. Positive TTF1 expressions in lung adenocarcinoma tissues are favorable prognostic parameters in patients with lung adenocarcinoma.