P53, RETINOBLASTOMA GENE-PRODUCT, AND CYCLIN PROTEIN EXPRESSION IN HUMAN PAPILLOMAVIRUS VIRUS DNA-POSITIVE CERVICAL INTRAEPITHELIAL NEOPLASIA AND INVASIVE CANCER

Human papillomavirus interacts with cyclin protein and tumor suppresso r genes, p53, and retinoblastoma gene (Rb). Expression of these gene p roducts was examined in 69 formalin-fixed, paraffin-embedded cervical biopsies by immunohistochemistry utilizing antibodies against p53, Rb, and proliferating cell nuclear antigen (PCNA) and by human papillomav irus DNA in-situ hybridization assays, Samples selected for this study included 27 normal/reactive atypia cases that were all human papillom avirus DNA in-situ hybridization negative, 37 cervical intraepithelial neoplasia (GIN) lesions, and 5 invasive carcinomas, The CIN and invas ive carcinoma cases were all human papillomavirus DNA in-situ hybridiz ation positive, p53 protein expression was detected in approximately o ne-third of the reactive atypia and CIN lesions and in 60% of invasive cancers, Neither the amount or the location of p53 staining was corre lated with the histologic diagnosis, Rb staining was more frequently f ound in the CIN/invasive carcinoma cases compared to the normal/reacti ve atypia samples (39/42 [93%] versus 21/27 [78%], respectively; P < 0 .05 by chi(2)). PCNA staining was detected in virtually all samples te sted, However, the location of both PCNA and Rb staining differed when the normal/ reactive atypia cases were compared to the CIN cases, Onl y 10% of the former group demonstrated Rb staining throughout the basa l two-thirds layer or full thickness of the epithelium compared with 6 5% of the latter group (P < 0.001 by chi(2)). Likewise, PCNA staining of the basal two thirds or full-thickness of the epithelium was found in only 58% of normal/reactive atypia cases, but in 97% of the CIN gro up (P < 0.001), Our results suggest that the location of Rb and PCNA s taining is quite different between normal/reactive atypia cervical bio psies and CIN lesions.