Cyclin-D1 expression in human renal-cell carcinoma

Cyclin-DI over-expression represents one of several common alterations in t he GI-S transition associated with malignancies. Conclusive evidences indic ate that cyclin DI is a proto-oncogene and the gene is amplified or rearran ged in different tumour types. Since very little is known about aberrations in the G(I)-S transition in human renal-cell carcinoma (RCC), we have char acterized the expression of cyclin DI in 80 human renal-cell carcinomas and 12 normal kidney cortex tissues using Western blotting, The cyclin-DI-prot ein content varied considerably and 75% of the tumours expressed higher lev els than normal kidney cortex, in contrast to 25% of the tumours either lac king cyclin DI or with low protein levels. Although it is difficult to defi ne aberrant expression of cyclin DI, the results might indicate that the pr oto-oncogene was activated in a sub-set of RCC. It is also possible that lo w expression of cyclin DI represents an aberrant down-regulation of the pro tein. Immunohistochemical assessment of cyclin DI in a sub-set of the tumou rs showed large variations in the fraction of cyclin-DI-positive cells, sup porting the Western-blot analyses. Surprisingly, cyclin-Dr expression did n ot correlate with proliferation determined by Ki-67-antigen expression or S -phase analyses. In non-papillary renal-cell carcinomas, high cyclin-DI exp ression was associated with a diploid DNA profile and smaller tumour size, bur there was no association between cyclin-DI expression and tumour stage or nuclear grade. In nonpapillary tumours, high cyclin-DI expression was fu rther significantly associated with a better prognosis according to univari ate and multivariate analyses (p = 0.005 and 0.002 respectively), as compar ed with highly aggressive tumours with low cyclin-DI levels. Int J. Cancer (Pred. Oncol) 84:268-272, 1999. (C) 1999 Wiley-Liss, Inc.