Expression of TGFbeta type-II receptor in association with markers of proliferation and apoptosis in premalignant lung lesions

Abstract

Background: Analysis of the early molecular abnormalities that play an oncogenic role in the progression of pulmonary neoplasia may lead to the identification of useful markers for early detection and prognosis. In normal squamous epithelium, transforming growth factor beta (TGFbeta) regulates cell growth and differentiation via specific membranous receptors and intracellular signaling molecules (Smads). The authors previously observed that, in head and neck squamous cell carcinoma, the expression of the TGFbeta type II receptor (TbetaR-II) decreases as tumors become less differentiated and more biologically aggressive.

Methods: In this pilot study of 48 premalignant bronchoepithelial lesions, the authors evaluated the expression of TbetaR-II and 2 proliferation markers (Ki-67 and MCM2), and the amount of early DNA fragmentation as evidence of apoptosis.

Results: The authors observed that the progression of premalignant lesions toward carcinoma in situ is accompanied by a decrease in TBR II expression and apoptosis and an increase in the expression of Ki-67 and MCM2.

Conclusions: These results suggested that the TGFbeta pathway may be impaired early in the neoplastic process and that a combination of selected markers can provide a useful profile to detect preneoplastic changes in individuals at high risk for developing pulmonary carcinoma.