Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis

Abstract

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 examined expression of cyclin D1 in 212 primary tumours of five histogenetically distinct types by immunohistochemistry and found strong aberrant accumulation of the protein in 21%, and a moderate overabundance in further 25% of cases. While the abnormalities were more frequent in carcinomas of the breast, i.e. the cancer type known for cyclin D1 gene amplification, aberrant expression was also seen in significant subsets of colorectal cancers, soft tissue sarcomas, uterine carcinomas and malignant 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 lesions (n = 51) of several tumour types. The specificity of the immunohistochemical data was supported by immunoblotting analysis of tissue and tumour lysates, and the tumour-specific over-expression was confirmed by computer-assisted image analysis. These observations suggest that alterations of cyclin D1 expression represent a common feature of malignancies of diverse histogenesis and indicate that both the spectrum of tumour types and the frequency of cyclin D1 aberrations significantly exceed previous estimations based on genetic analyses.