Overexpression of cyclin D1 in nonmelanocytic skin cancer

Although the overexpression of cyclin D1 has been believed to play importan t roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen's dise ase (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell c arcinoma (BCC), were investigated immunohistochemically using monoclonal an tibody to cyclin D1 by the LSAB method, to assess the expression of cyclin DI in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respective ly. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, onl y 2 cases, 1 of SCC and of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dyspl asia of BCC was correlated with age. Expression of cyclin D1 markedly incre ased from normal skin through dysplasia to BOD, but was not significantly r elated to the degree of SCC differentiation. These findings demonstrate tha t the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is n ot increased. Comparison with the results for p53 protein expression in the se tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 y ears old. These findings suggested the hypothesis that prior aberrant p53 e xpression may affect or regulate the overexpression of cyclin D1.