Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung

Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplasti c bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to ne onatal death with pulmonary hypoplasia, We evaluated retrospectively the pr evalence and clinical significance of TIT-1 immunoreactivity in 222 patient s with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other marker s of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immuno reactivity was documented by using the commercially available monoclonal an tibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcin omas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but n ot squamous cell carcinomas, TTF-1 immunoreactivity correlated significantl y with microvessel density (p = 0.04) and inversely with the tumor prolifer ation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-imm unoreactive adenocarcinomas showed a trend for a size less than 3 cm(p = 0. 08). TTF-1 expression was not related to specific growth patterns, tumor gr ade, or tumor cell typing. TTF-1 immunoreactivity did not significantly aff ect patient survival, although patients with more than 75% immunoreactive n eoplastic cells showed a trend for longer overall and disease-free survival . Our findings suggest that TTF-1 could be involved in the development of s mall pulmonary adenocarcinomas, but it has not prognostic implications in p atients with stage I NSCLC.