Cyclin-D1 expression in human renal-cell carcinoma

Cyclin-DI over-expression represents one of several common alterations in the GI-S transition associated with malignancies. Conclusive evidences indicate that cyclin DI is a proto-oncogene and the gene is amplified or rearranged 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 characterized the expression of cyclin DI in 80 human renal-cell carcinomas and 12 normal kidney cortex tissues using Western blotting, The cyclin-DI-protein content varied considerably and 75% of the tumours expressed higher levels than normal kidney cortex, in contrast to 25% of the tumours either lacking cyclin DI or with low protein levels. Although it is difficult to define aberrant expression of cyclin DI, the results might indicate that the proto-oncogene was activated in a sub-set of RCC. It is also possible that low expression of cyclin DI represents an aberrant down-regulation of the protein. Immunohistochemical assessment of cyclin DI in a sub-set of the tumours showed large variations in the fraction of cyclin-DI-positive cells, supporting the Western-blot analyses. Surprisingly, cyclin-Dr expression did not correlate with proliferation determined by Ki-67-antigen expression or S-phase analyses. In non-papillary renal-cell carcinomas, high cyclin-DI expression 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 further significantly associated with a better prognosis according to univariate and multivariate analyses (p = 0.005 and 0.002 respectively), as compared with highly aggressive tumours with low cyclin-DI levels. Int J. Cancer (Pred. Oncol) 84:268-272, 1999. (C) 1999 Wiley-Liss, Inc.