P53 EXPRESSION IN SKIN CARCINOGENESIS AND RELATIONSHIPS TO CELL-PROLIFERATION AND TUMOR-GROWTH

The immunoreactivity of p53 protein was studied in relation to tumour development, histopathological characteristics, cell proliferation, an d basement membrane organisation following the induction of skin carci nogenesis in tumour-sensitive and -resistant mouse strains by ultravio let (UV) irradiation or 7,12-dimethylbenz(a)anthracene (DMBA). In non- neoplastic skin exposed to UV irradiation or DMBA, p53 immunoreactivit y was observed in nearly 50% of the basal layer cells. These cells wer e morphologically and histochemically indistinguishable from the p53-n egative cells, occurring similarly in the tumour-producing and the tum our-negative mouse strains and regardless of subsequent tumour formati on. In induced epidermal hyperplasia and in benign tumours, p53-positi ve and proliferating cells constituted 40-50% of all cells in the basa l layer, while superficial cells were p53 negative. In dysplastic epid ermis, p53-positive cells and proliferating cells were seen in all cel l layers. In the case of squamous cell carcinomas, p53-positive prolif erating cells in differentiated neoplasms were localised close to the basement membrane and, more frequently, in border areas showing invasi on and basement membrane destruction. In horn cysts, centrally located cells were nonproliferating and p53 negative. In moderately different iated neoplasms, proliferating cells were located closer to the baseme nt membrane, while p53-positive cells were distributed diffusely in th e neoplasm. In poorly differentiated neoplasms, p53-positive cells wer e more common than proliferating cells and were arranged in a diffuse pattern. The results showed that the number and location of p53-positi ve cells depended upon histology, with a close relationship to tumour type and degree of malignancy, but not on the mode of induction, nor o n the animal strain or the relationship to subsequent tumour formation . (C) 1998 Elsevier Science Ltd. All rights reserved.