Cyclin-D1 expression in human renal-cell carcinoma

Abstract

Cyclin-D1 over-expression represents one of several common alterations in the G1-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 G1-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 nonpapillary 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.