Cyclin‐D1 expression in human renal‐cell carcinoma

Cyclin‐D1 over‐expression represents one of several common alterations in the G 1 ‐S transition associated with malignancies. Conclusive evidences indicate that cyclin D1 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 1 ‐S transition in human renal‐cell carcinoma (RCC), we have characterized the expression of cyclin D1 in 80 human renal‐cell carcinomas and 12 normal kidney cortex tissues using Western blotting. The cyclin‐D1‐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 D1 or with low protein levels. Although it is difficult to define aberrant expression of cyclin D1, 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 D1 represents an aberrant down‐regulation of the protein. Immunohistochemical assessment of cyclin D1 in a sub‐set of the tumours showed large variations in the fraction of cyclin‐D1‐positive cells, supporting the Western‐blot analyses. Surprisingly, cyclin‐D1 expression did not correlate with proliferation determined by Ki‐67‐antigen expression or S‐phase analyses. In non‐papillary renal‐cell carcinomas, high cyclin‐D1 expression was associated with a diploid DNA profile and smaller tumour size, but there was no association between cyclin‐D1 expression and tumour stage or nuclear grade. In non‐papillary tumours, high cyclin‐D1 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‐D1 levels. Int. J. Cancer (Pred. Oncol.) 84:268–272, 1999. © 1999 Wiley‐Liss, Inc.