EXPRESSION OF P53 AND BCL-2 IN ADENOMAS AND COLORECTAL-CARCINOMA

Recent publications have associated p53 and bcl-2 genes in the process of neoplastic transformation. As the colonic adenoma-carcinoma sequen ce is an adequate natural model for carcinogenesis, it was considered interesting to analyze the expression of bcl-2 and p53 in these neopla sms. Seventy three adenomatous polyps (adenomas) and 60 adenocarcinoma s of the colon and rectum were studied. Adenomas showed mild dysplasia in 16, moderate in 27, severe in 15 and focal carcinoma in the remain ing 15. Adenocarcinomas surpassed the deep muscle layer in every case and were moderately differentiated. The studied gene expression was an alyzed immunohistochemically using antibodies bcl-2 from Dako and p53 from Novocastra, both at a 1:100 dilution. Cytoplasmic stain for bcl-2 and nuclear stain for p53 above 10% of the cells were considered posi tive for each gene respectively. Results showed that there was accumul ation of p53 protein in 26/58 (45%) adenomas with different grades of dysplasia. This result is similar to the reactivity found in adenomas with focal carcinoma where 8/15 (53%, p = 0.4) were positive but diffe rent from adenocarcinomas which were positive in 47/60 (78%, p = 0.000 1). Regarding bcl-2, positivity was found in 53/73 (73%) of all the ad enomas whereas adenocarcinoma showed expression in 14/60 (23%, p = 0.0 000). When adenomas were grouped according to their degree of dysplasi a and the existence of focal carcinoma, a diminishing frequency of rea ctivity for bcl-2 was found and when adenomas with three different gra des of dysplasia were fused together, 47/58 (81%) were positive and th is was compared with adenomas having focal carcinoma, 6/15 (40%) and w ith adenocarcinoma, 14/60 (23%), they showed significant differences ( p = 0.001 and p = 0.0000 respectively). The analysis of the frequency of expression for both genes studied in the different lesions describe d yielded an inverse relation between them. This study allows the conc lusion that the expression of bcl-2 is an early event in carcinogenesi s and that it is replaced by nutation of p53 as the neoplastic change progresses.