EXPRESSION OF P53 PROTEIN RELATED TO THE PRESENCE OF HUMAN PAPILLOMAVIRUS (HPV) DNA IN GENITAL CARCINOMAS AND PRECANCER LESIONS

The E6 protein of the high-risk human papillomavirus (HPV) types 16 an d 18 is capable of complexing with the wild-type p53 tumor suppressor gene product, leading to loss of the normal p53 function as an anti-on gogene, whereas the low-risk HPV types 6 and 11 lack this binding prop erty. The malignant potential of HPV 16 and 18 has been ascribed to th is complexing of E6 with p53, which regularly leads to undetectable ex pression of the latter in HPV-positive lesions. To assess the role of p53 in HPV-associated genital carcinogenesis, the expression of p53 pr otein was studied immunohistochemically in 22 genital carcinomas and p recancer lesions: 8 vulvar carcinomas, 1 VIN (vulvar intraepithelial n eoplasia), 5 cervical carcinomas and 8 CIN (cervical intraepithelial n eoplasia) using monoclonal antibody PAb 1801. Presence of HPV was demo nstrated by PCR using HPV consensus primers, and amplified HPV-DNA was digested with the restriction enzymes giving distinct patterns for va rious HPV-types in gel electrophoresis. HPV-typing was confirmed by in situ hybridization with biotinylated DNA probes. Altogether, 17 of th e 22 specimens (77%) showed p53 expression: 67% of the precancer lesio ns and 83% of carcinomas. Expression was more frequent (89%) in the vu lvar than (70%) in cervical lesions. Using PCR, HPV DNA was detected i n 19122 (86 %) of the samples. The following HPV types were identified : HPV 6 (2 samples), HPV 11 (3 cases), HPV 16 (5 cases), HPV 33 (3 cas es), and 6 contained unidentified HPV types. All HPV DNA-negative spec imens showed p53 expression. Of the 19 HPV DNA-positive lesions, 5 wer e p53-negative, three of these being HPV 16 positive CIN lesions. The remaining two HPV 16 lesions were invasive carcinomas with a weak p53 expression. HPV 6 and 11-positive lesions showed a weak p53 expression more frequently than HPV-negative cases and HPV 33 lesions. The resul ts indicate that p53 expression is detectable, but it is less frequent and less intense in HPV DNA-positive genital precancer lesions and ca rcinomas (particularly those with HPV 16 DNA) as compared with HPV DNA -negative lesions.