Objective: To observe the expression of thyroid transcription factor-1 (TTF-1) mRNA in human normal adult type II alveolar epithelial cells, embryonic alveolar epithelial cells, and primary lung carcinoma and lymph nodes, thereby exploring the role of TTF-1 mRNA expression in the tumorigenesis, development and metastasis of lung carcinoma.
Methods: TTF-1 mRNA was detected using tissue microarray and in situ hybridization in 1320 different paraffin-embedded tissue specimens. The intensity of TTF-1 mRNA in these tissues was assessed quantitatively using Leica Q500MC image analysis system.
Results: TTF-1 mRNA expression was significantly less intense in embryonic lung than in normal adult lung tissues (P= 0.000), and the two tissues both had significantly greater expression than lung adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma (P=0.000). Lung adenocarcinoma and small cell carcinoma, with similar expression intensity (P= 0.068), showed stronger expression than squamous cell carcinoma and large cell carcinoma (P=0.000), and squamous cell carcinoma showed stronger expression than large cell carcinoma (P=0.018). In lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma, the intensity of TTF-1 mRNA expression was stronger in lymph node metastases than in the primary foci (P=0.003, P=0.000, P=0.019, respectively). The lymph node metastases had more intense expression than the primary foci of small cell lung carcinoma (P=0.078). The intensity of TTF-1 mRNA expression was greater in primary lung carcinomas with lymph node metastases than in those without metastases (P=0.026). Tumors of TNM stage II-IV had stronger expression than those of stage I (P=0.010). The intensity of TTF-1 mRNA expression was not associated with the patients' gender or the general types and differentiation of the tumor.
Conclusion: The amount of TTF-1 mRNA expression lowers in the order of normal adult lung, embryonic lung and lung carcinoma tissues. In lung carcinomas, TTF-1 mRNA expression differs between the histological types, high in lung adenocarcinoma and small cell carcinoma and rather low in squamous cell carcinoma and large cell carcinoma. Strong expression of TTF-1 mRNA often indicates high likeliness of lung carcinoma metastasis, and highlights the high metastatic potentials of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.