COMBINED AND SEQUENTIAL EXPRESSION OF P53, RB, RAS AND BCL-2 IN BRONCHIAL PRENEOPLASTIC LESIONS

Aims and background: Several simple molecular abnormalities have been detected rn bronchial preneoplastic lesions, but the simultaneous pres ence of these alterations has been scarcely investigated. Methods: We studied, by an immunohistochemical method, the expression of p53, Rb, Ras and Bcl-2 in 65 samples from surgical specimens and diagnostic bio psies selected for the presence of preneoplastic changes in the bronch ial epithelium. To perform an analysis of the combined expression of a ll markers in the same areas, we accurately mapped every consecutive s ection on which immunohistochemical reactions were performed, subdivid ing each specimen into 25x microscopic fields, which allowed good topo graphical mapping. Results: It was found that the frequency of p53-pos itive and Rb-negative microscopic fields was directly related to the m orphological grading of lesions. On the other hand, Ras expression cha racterized high-grade lesions not Showing squamous differentiation (no n-squamous Cis). Regarding Bcl-2 expression, only slight differences i n positivity distribution were found between the different lesions. Mo re interesting was the parallel evaluation of all markers in the same areas: one of the main patterns, found to be correlated with the sever ity of histopathological features, was characterized by combined p53 h yperexpression/Rb hypoexpression; furthermore, when Ras and Bcl-2 hype rexpression were superimposed to the above pattern, the former mainly characterized non-squamous Cis, while the latter was present only in h igh-grade squamous lesions. However, the most frequently encountered p attern did not show any alteration of the studied markers, suggesting that other mechanisms could be involved in bronchial carcinogenesis. C onclusions: The detection of combined molecular abnormalities in bronc hial preneoplasia could clarify the steps involved in lung carcinogene sis; furthermore, a simple and inexpensive method, such as immunohisto chemistry, could be routinely applied also to cytologic specimens in o rder to detect those lesions, or patients, that are prone to progressi on towards lung cancer.