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 neoplastic 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 neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients 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 markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive 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 grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.
Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy. giuseppe.pelosi@ieo.it
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Pelosi
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Fraggetta
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Pasini
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Maisonneuve
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Sonzogni
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Iannucci
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Terzi
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Bresaola
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Valduga
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Viale
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors