Thyroid transcription factor-1 (TTF-1) is a 38-kDa nuclear protein expressed in thyroid follicular cells, in human fetal lung, and, after birth, in Type II epithelial cells of alveoli and in a subset of bronchial cells. Expression of TTF-1 was documented in neoplasms arising from cells that normally produce this transcription factor. In the present study, a series of surgically resected non-small cell lung carcinomas (NSCLCs) was evaluated for the expression of TTF-1 protein, and the correlation between TTF-1 expression and patient survival was retrospectively tested. Ninety-six patients with primary NSCLC underwent surgical resection between 1987 and 1992. All of the tissue specimens from these patients were examined for TTF-1 protein expression by immunohistochemical analysis. Tumor immunoreactivity for TTF-1 was categorized into three groups (-, +, and ++), according to the percentage of reactive cells. The relationship between TTF-1 expression and postsurgical survival was analyzed for 88 patients [60 squamous cell carcinomas (SCCs) and 28 adenocarcinomas (ACs)]. TTF-1 stain was always limited to nuclei. Of the 96 specimens of NSCLC, 59 (61%) were scored as -, 20 (21%) as +, and 17 (18%) as ++. TTF-1 expression was significantly higher in ACs than in SCCs (P < .0001). Survival curves among the -, +, and ++ groups were significantly different (log rank test, P = .04). Multivariate analysis showed that NSCLCs in the ++ group were associated with a poor prognosis (P = .009), independent of node (P = .01) or stage status (P = .0006). When subsets of patients with SCC and with AC were separately analyzed, TTF-1 was found to have an independent prognostic value only in patients with SCC (P = .04). The results of this study suggest that immunoreactivity for TTF-1 in NSCLC closely relates to clinical outcome, especially in patients with SCC.
