Immunohistochemical expression of bcl-2 and p53 oncoproteins: Correlation with Ki67 proliferation index and prognostic histopathologic parameters in colorectal neoplasia

The bcl-2 oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell ly mphoma with t(14,18) and subsequently found in other malignant and premalig nant lesions. Alteration of the normal controls of cell proliferation is al so a significant factor in the multistep process of tumorigenesis. The prol iferative activity of a given lesion is commonly evaluated by MIB1, a monoc lonal antibody to Ki67 proliferation antigen, Mutation of the p53 gene is c onsidered the most common genetic aberration in colorectal cancer. Immunohi stochemical (IHC) staining expression of bcl-2, Ki67, and p53 was retrospec tively investigated in a series of 52 colorectal carcinomas and 56 adenomas , The aim of the study was twofold: (i) to investigate any correlation betw een MIB1, p53, and bcl-2 immunostaining expression in colonic adenomas and carcinomas and (ii) to identify any relation between these markers and seve ral histopathologic parameters including tumor size, pathologic stage, lymp h node metastasis, angiolymphatic invasion, tumor grade, and differentiatio n in colon carcinomas, bcl-2 was consistently higher in adenomas than in ca rcinomas. There were 44 of 56 (78.6%) adenomas and 27 of 52 (51.9%) carcino mas positive for bcl-2 (P = 0.004). The mean Ki67 labeling index (LI) was 3 0.05 +/- 7.6 and 38.12 +/- 11.01 in adenomas and carcinomas, respectively ( P = 0.0001). p53 was significantly higher in carcinomas (35 of 52 [67.3%]) than in adenomas (18 of 56 [32.1%]) (P = 0.0004). Expression of bcl-2 in ca rcinoma was associated with a lower p53 levels and lower mean Ki67 LI and w ith favorable histopathologic parameters. Higher p53 and Ki67 values were a ssociated with prognostically poor histopathologic features (differentiatio n and Duke's stage). We conclude that, in contrast to p53 and Ki67, bcl-2 o ncoprotein expression is probably an early step in the process of colon car cinogenesis, and its expression may be associated with favorable pathologic parameters. Furthermore, an inverse relation exists between p53 and Ki67, and bcl-2 IHC expression in colonic neoplasia. Evaluation of bcl-2, p53, an d Ki67 IHC expression in colonic carcinoma may be of value in predicting th e clinical course in these patients.