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

Abstract

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.

• Authors: G Pelosi, F Fraggetta, F Pasini, P Maisonneuve, A Sonzogni, A Iannucci, A Terzi, E Bresaola, F Valduga, C Lupo, G Viale
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 25 Issue 3 Pg. 363-72 (Mar 2001) ISSN: 0147-5185 [Print] United States
• PMID: 11224607 (Publication Type: Journal Article)

Chemical References

• NKX2-1 protein, human
• Nuclear Proteins
• Thyroid Nuclear Factor 1
• Transcription Factors

Topics

• Adenocarcinoma (blood supply, metabolism, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Adenosquamous (blood supply, metabolism, mortality, pathology)
• Carcinoma, Large Cell (blood supply, metabolism, mortality, pathology)
• Carcinoma, Non-Small-Cell Lung (blood supply, metabolism, mortality, pathology)
• Carcinoma, Squamous Cell (blood supply, metabolism, mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (blood supply, metabolism, mortality, pathology)
• Male
• Microcirculation
• Middle Aged
• Neoplasm Staging
• Nuclear Proteins (metabolism)
• Retrospective Studies
• Survival Rate
• Thyroid Nuclear Factor 1
• Transcription Factors (metabolism)