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 suppressor genes, p53, and retinoblastoma gene (Rb). Expression of these gene products 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 papillomavirus DNA in-situ hybridization assays. Samples selected for this study included 27 normal/reactive atypia cases that were all human papillomavirus DNA in-situ hybridization negative, 37 cervical intraepithelial neoplasia (CIN) lesions, and 5 invasive carcinomas. The CIN and invasive carcinoma cases were all human papillomavirus DNA in-situ hybridization positive. p53 protein expression was detected in approximately one-third of the reactive atypia and CIN lesions and in 60% of invasive cancers. Neither the amount or the location of p53 staining was correlated with the histologic diagnosis. Rb staining was more frequently found in the CIN/invasive carcinoma cases compared to the normal/reactive atypia samples (39/42 [93%] versus 21/27 [78%], respectively; P < 0.05 by chi 2. PCNA staining was detected in virtually all samples tested. However, the location of both PCNA and Rb staining differed when the normal/reactive atypia cases were compared to the CIN cases. Only 10% of the former group demonstrated Rb staining throughout the basal two-thirds layer or full thickness of the epithelium compared with 65% of the latter group (P < 0.001 by chi2). 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 group (P < 0.001). Our results suggest that the location of Rb and PCNA staining is quite different between normal/reactive atypia cervical biopsies and CIN lesions.