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, including 46 cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohistochemically using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun exposure and ageing, and growth and differentiation of skin 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 morphologically normal epidermis adjoining cancers. Sun exposure was statistically correlated with the p53 immunostaining scores in morphologically normal epidermis of the three skin cancers and in cancer nests of SCC and BCC. The positivity and score of p53 protein often differed significantly among the three types of cancer, especially in regions of dysplasia. Interestingly, differentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in morphologically normal epidermis. It seems that the accumulation of p53 protein plays a part in precancerous lesions and in the genesis of more highly differentiated types of skin cancer and affects mainly the growth of tumour cells rather than their differentiation. For BCC, however, age was significantly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly related to sun exposure, that the expression of p53 in BCC is an age-dependent process, and that the early accumulation of p53 protein may be a useful predictor for the detection of nonmelanocytic skin cancer.