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

Abstract

The bcl-2 oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18) and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly evaluated by MIB 1, a monoclonal antibody to Ki67 proliferation antigen. Mutation of the p53 gene is considered the most common genetic aberration in colorectal cancer. Immunohistochemical (IHC) staining expression of bcl-2, Ki67, and p53 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas. The aim of the study was twofold: (i) to investigate any correlation between MIB 1, p53, and bcl-2 immunostaining expression in colonic adenomas and carcinomas and (ii) to identify any relation between these markers and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angiolymphatic invasion, tumor grade, and differentiation in colon carcinomas. bcl-2 was consistently higher in adenomas than in carcinomas. There were 44 of 56 (78.6%) adenomas and 27 of 52 (51.9%) carcinomas positive for bcl-2 (P = 0.004). The mean Ki67 labeling index (LI) was 30.05 +/- 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 carcinoma was associated with a lower p53 levels and lower mean Ki67 LI and with favorable histopathologic parameters. Higher p53 and Ki67 values were associated with prognostically poor histopathologic features (differentiation and Duke's stage). We conclude that, in contrast to p53 and Ki67, bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, 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, and Ki67 IHC expression in colonic carcinoma may be of value in predicting the clinical course in these patients.