title: p53 antigen in cervical condylomata, intraepithelial neoplasia, and carcinoma: relationship to HPV infection and integration.
abstract: It has been proposed that wild-type p53 cell-regulating functions are annulled in human cervical carcinomas, either by mutations in the human papillomavirus (HPV)-negative cases or as a consequence of their complexing with HPV E6. The aim of this study was to test this hypothesis on 39 fresh cervical biopsies by p53 immunocytochemistry (ICC) with antibody PAb 240 and with NISH (non-isotopic in situ hybridization) and PCR (polymerase chain reaction) for HPV detection. p53 protein was present in the basal layer of pure wart virus infection; the basal to middle third of CIN (cervical intraepithelial neoplasia); in 19/22 (86 per cent) HPV-positive cervical carcinomas, ten of which contained integrated HPV; and in 4/8 (50 per cent) HPV-negative cervical carcinomas. Dual detection of p53 antigen and HPV 16 DNA in the same sections demonstrated either p53 protein or integrated HPV 16 alone in the majority of cells. Co-localization of both signals was only evident in isolated cells. These data suggest that PAb 240 immunoreactivity is not mutant-specific. They are, however, consistent with the conformation hypothesis which proposes that wild-type p53 changes from a suppressor (PAb 240-negative) to a promoter (PAb 240-positive) form during cell growth response. Hence, according to this hypothesis, p53 protein expression may represent either the wild-type promoter form or mutant p53 protein, both of which share the same conformation. This may explain co-localization of p53 and HPV in some tumours. However, the absence of p53 protein in 50 per cent HPV-negative squamous cell carcinomas suggests that not all HPV-negative tumours accumulate p53 protein.
authors.affiliation: University of Oxford, Nuffield Department of Pathology and Bacteriology, John Radcliffe Hospital, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Cooper
authors.forename: C S
authors.initials: CS
authors.lastname: Herrington
authors.forename: M F
authors.initials: MF
authors.lastname: Evans
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: J O
authors.initials: JO
authors.lastname: McGee
mesh_terms: D003218:Condylomata Acuminata / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D027383:Papillomaviridae; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000276:immunology; D014412:Tumor Virus Infections / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000382:microbiology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000382:microbiology
chemical_list: D016159:Tumor Suppressor Protein p53