The Expression and Correlation of Cyclin E, P21WAF1Protein and P53 Variant Protein in Colorectal Adenoma and Carcinoma

ABSTRACT

Cyclins are proteins that activate different cyclin-dependent kinases(CDKs) and promote the cell cycles. Their correlations with several human cancers have been identified. Cyclin E, as one of G1 cylins, produces DNA replication through the progression of cell cycle G1 --> S phase. In contrast, cyclin-dependent kinase inhibitors(CDKI) bound with cyclin E-cdk2 complex control the cell cycle and inhibit the cell proliferation. P21(WAF1) proteins, which are CDKIs, are transcripted by a p53 gene and participate in the cell cycle inhibition. Variant p53 proteins produced by a mutated p53 gene lose the ability to control of the cell cycle resulting in cell proliferation. This study is aimed to reveal the expressions of cyclin E, p21(WAF1) protein, p53 variant protein in colorectal adenomas and carcinomas, and also reveal their correlations in the process of carcinogenesis. Twenty-one colorectal adenomas or adenomatous polyps, and thirty colorectal carcinoma tissues were obtained by operative resections or endoscopic polypectomies. Immuno histochemical stains of the above-mentioned three proteins and a statistical analysis of their correlations were made. The results were as follows 1. P21 proteins were expressed in the upper-one third layer of all normal colonic mucosa, but cyclin E and variant p53 protein were not identified. 2. Cyclin E was expressed in 23.8% of adenomas and 76.7% of carcinomas. Variant p53 protein was expressed in 71.4% of adenomas and 83.3% in carcinomas. The degree of positivity of variant p53 expression was correlated with cancer staging. P21 protein was expressed in all adenomas, similar to normal mucosa, but was not expressed in 43.3% of carcinomas. 3. Expression of cyclin E was increased as to the positivity of variant p53 proteins but the correlations of p21 proteins and cyclin E, and p21 proteins and variant p53 proteins were not identified. Cancer staging was not correlated with the expressions of the three proteins. In conclusion, it can be thought that the overexpression of cyclin E and variant p53 proteins, and the loss of p21 proteins are related with the colorectal carcinogenesis. We can also identify the relationship of cyclin E and variant p53 proteins.