[Quantitative analysis of thyroid transcription factor-1 mRNA expressions in primary lung cancer and its metastatic foci].
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.


CONCLUSIONS
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.
Bai
Xiao-Yan
XY
Department of Pathology, Southern Medical University, Guangzhou 510515, China. baixyn@yahoo.com
Shen
Hong
H
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors