A POSSIBLE ROLE FOR HUMAN PAPILLOMAVIRUSES AND C-MYC, C-HA-RAS, AND P53 GENE ALTERATIONS IN MALIGNANT CUTANEOUS LESIONS FROM RENAL-TRANSPLANT RECIPIENTS

Several years after transplantation, renal transplant recipients devel op numerous cutaneous squamous cell carcinomas (SCC), in which human p apillomaviruses (HPV) may be detected. Alterations in c-myc, c-Ha-ras, and p53 genes were studied in 34 SCC, in correlation with the presenc e of HPV. In situ hybridization (ISH) and polymerase chain reaction (P CR) showed that many SCC contained several HPV types infecting differe nt foci of epithelial cells. Using Southern blot and ISH, c-myc and/or c-Ha-ras gene amplification was detected in 7/13 SCC tested. With PCR and oligoprobe hybridization, a GGC --> GAC mutation was found at cod on 12 of c-Ha-ras gene in 1/21 SCC tested, while no mutation was detec ted at codon 61. Using immunohistochemistry, p53 protein expression wa s detected either along the basal cell layer or spotted in foci of bas al cells. Our results show an abnormal distribution of HPV types in SC C from renal transplant recipients, and alterations of c-myc, c-Ha-ras , and p53 genes without any direct link with the presence of any studi ed HPV type. Thus, viral infection and oncogene activation may represe nt factors involved in the etiology of skin SCC from transplant recipi ents.