ACCUMULATION OF P53 IS ASSOCIATED WITH TUMOR PROGRESSION IN CUTANEOUSLESIONS OF RENAL-ALLOGRAFT RECIPIENTS

Renal allograft recipients suffer from a markedly increased susceptibi lity to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the ass ociated genetic events. In this study we initially employed immunocyto chemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent c ontrols. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignan t keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma diff ered significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (a n older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of s quamous cell carcinomas. These differences were not statistically sign ificant. Morphologically, p53 immunoreactivity strongly associated wit h areas of epidermal dysplasia and the abundance of staining correlate d positively with the severity of dysplasia. These data suggest that p 53 plays a role in skin carcinogenesis and is associated with progress ion towards the invasive state. No correlation was observed between ac cumulated p53 and the presence of human papillomavirus (HPV) DNA in an y of the lesions. Single-strand conformational polymorphism analysis ( exons 5-8) was used to determine the frequency of mutated p53 in 28 ma lignancies with varying degrees of immunopositivity. p53 mutations wer e found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained a nd none where < 10% of cells were stained. These data imply that facto rs other than p53 gene mutation play a part in accumulation of p53 in skin cancers.