Expression of p57/Kip2 protein in hepatocellular carcinoma

Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. In the present study, we investigated the expression of p57 (Kip2) in 90 hepatocellular carcinomas and 66 noncancerous lesions. The average p57 labeling index in noncancerous lesions was 72.3 +/- 19.7. The labeling index significantly decreased (p < 0.0001) in hepatocellular carcinoma (54.9 +/- 19.7). It was significantly lower in hepatocellular carcinoma cases with high biological aggressiveness such as advanced stage (p = 0.0041), poor differentiation (p < 0.0001), larger size (p = 0.0400), portal invasion (p < 0.0001), satellite tumor (p = 0.0023), high proliferating activity (p = 0.0002) and cyclin D(1) overexpression (p = 0.0416). Furthermore, cases with low p57 expression showed worse outcomes for disease-free survival in univariate analysis (p = 0.0235), although p57 expression could not be recognized as an independent prognostic factor. These findings suggest that p57 contributes to the downregulation of cell proliferation and to the progression of hepatocellular carcinoma.