Detection of p53 and histopathological classification of skin tumours induced by halogen lamps in hairless mice.

Abstract

Skin lesions induced by exposure of three strains of female hairless mice to the light emitted by uncovered halogen quartz lamps were subjected to histopathological analysis. We examined 170 representative specimens out of a total of 597 skin lesions, i.e. 38 out of 74 SKH-1 mice, 110 out of 472 MF-1 mice, and 42 out of 51 C3H mice. The results provided evidence of various types of alterations, including preneoplastic changes, such as epidermal hyperplasia, and benign tumours, such as papillomas, as well as tumours with an increasing degree of malignancy, i.e., keratoacanthoma-like tumours, appendage/basal tumours, actinic keratoses/carcinomas in situ, and squamocellular carcinomas. SKH-1 was the most sensitive strain to the far-ultraviolet wavelengths delivered by halogen lamps, as shown not only by the shortest latency time and the highest multiplicity of skin lesions but also by the highest frequency of malignant tumours. Some areas of atypical melanocyte proliferation were only detected in C3H pigmented mice. Eighty-two of the lesions excised from MF-1 mice were additionally examined for p53 protein by immunohistochemical methods. Formalin-fixed, paraffin-embedded sections and frozen sections were analyzed in parallel by using polyclonal CM-1 antibody and monoclonal PAb240 antibody, respectively. A positive response for p53 was only observed in squamocellular carcinomas, and was related to the size of cancers; in fact, six out of 10 cancers of 10-30 mm in diameter were positive, whereas all 16 cancers of 2-9 mm in diameter were negative. All six positive squamocellular carcinomas were detected by using the CM-1 antibody, which recognizes both wild-type and mutant forms of p53 protein, and five of them were also positive with the PAb 240 antibody, which only recognizes the mutant form. Thus, p53 mutation appears to be a late event in the development of halogen-induced skin tumours in hairless mice, requiring a severe degree of malignancy and an advanced stage of the neoplastic mass growth.