THE ROLE OF P53 INACTIVATION IN HUMAN CERVICAL CELL-CARCINOMA DEVELOPMENT

We investigated the association between human papillomavirus (HPV) inf ection and p53 gene mutation in 47 primary uterine cervical cancers. H PV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaini ng four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both pri mary and recurrent tumours front four cases. In two of these cases, th e HPV genomes that were present in an episomal state in the primary tu mours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which s uggested the possibility that p53 inactivation was required in order t o maintain the aggressive behaviour in this cancer either by an HPV in fection or by a p53 gene mutation. No MDM2 gene amplification was obse rved in the tumours that carried neither HPV DNAs nor p53 gene mutatio ns.