CYCLIN D1 ONCOPROTEIN ABERRANTLY ACCUMULATES IN MALIGNANCIES OF DIVERSE HISTOGENESIS

Cyclin D1 is a cell cycle regulator essential for G1 phase progression and a candidate proto-oncogene whose deregulated expression has been implicated in pathogenesis of several types of cancer. We have examine d expression of cyclin D1 in 212 primary tumours of five histogenetica lly distinct types by immunohistochemistry and found strong aberrant a ccumulation of the protein in 21%, and a moderate overabundance in fur ther 25% of cases. While the abnormalities were more frequent in carci nomas of the breast, i.e. the cancer type known for cyclin D1 gene amp lification, aberrant expression was also seen in significant subsets o f colorectal cancers, soft tissue sarcomas, uterine carcinomas and mal ignant melanomas. Comparison of distinct stages of tumour progression showed concordant cyclin D1 patterns in the in situ vs invasive breast carcinoma components (n=37) and between primary and metastatic lesion s (n=51) of several tumour types. The specificity of the immunohistoch emical data was supported by immunoblotting analysis of tissue and tum our lysates, and the tumour-specific over-expression was confirmed by computer-assisted image analysis. These observations suggest that alte rations of cyclin D1 expression represent a common feature of malignan cies of diverse histogenesis and indicate that both the spectrum of tu mour types and the frequency of cyclin D1 aberrations significantly ex ceed previous estimations based on genetic analyses.