DIFFERENTIATION AND PROGRAMMED CELL DEATH-RELATED INTERMEDIATE BIOMARKERS FOR THE DEVELOPMENT OF NONSMALL CELL LUNG-CANCER - A PILOT-STUDY

Fifty samples of lung tissue from patients with non-small cell lung ca ncer were analyzed for the expression and localization of biomarkers r elated to squamous differentiation and programmed cell death. These ma rkers include tissue transglutaminase (tTG),keratinocyte transglutamin ase (kTG), involucrin, loricrin, and Bcl-2. We found that all of these markers are overexpressed in tumors as compared with histologically n ormal lung epithelium, where expression is minimal. Expression of the oncoprotein, Bcl-2, increased starting in squamous metaplasia and rema ined elevated in all lesions, including frank carcinoma. In contrast, expression of the other markers was elevated in the histologically abn ormal noninvasive lesions but was decreased somewhat in invasive malig nancy. In addition, we found that tTG, kTG, and Bcl-2, when expressed, were detected in mutually exclusive areas. These findings suggest tha t (1) these markers may prove useful, with more extensive testing and clinical correlation, in predicting risk for the development of lung c ancer; and (2) pulmonary carcinogenesis may result from the failure of differentiation and programmed cell death mechanisms in the presence of oncogene overexpression rather than through oncogene/tumor suppress or gene abnormalities alone. Copyright (C) 1998 by W.B. Saunders Compa ny.