Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer

Three hundred and sixteen patients with nonmelanocytic skin cancer, includi ng 46 cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohis tochemically using monoclonal antibody DO-7 to assess p53 protein accumulat ion related to sun exposure and ageing, and growth and differentiation of s kin cancer and its precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1% and 70.6%, respectively. p53-positive cells were present not only in cancer nests, but also in dysplastic and even morpholog ically normal epidermis adjoining cancers. Sun exposure was statistically c orrelated with the p53 immunostaining scores in morphologically normal epid ermis of the three skin cancers and in cancer nests of SCC and BCC. The pos itivity and score of p53 protein often differed significantly among the thr ee types of cancer, especially in regions of dysplasia. Interestingly, diff erentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, d emonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in mor phologically normal epidermis. It seems that the accumulation of p53 protei n plays a part in precancerous lesions and in the genesis of more highly di fferentiated types of skin cancer and affects mainly the growth of tumour c ells rather than their differentiation. For BCC, however, age was significa ntly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly relate d to sun exposure, that the expression of p53 in BCC is an age-dependent pr ocess, and that the early accumulation of p53 protein may be a useful predi ctor for the detection of nonmelanocytic skin cancer.