An immunohistochemical study of retinoblastoma gene product in normal, premalignant and malignant tissues of the uterine cervix.

The retinoblastoma gene was the first tumour suppressor gene identified that was altered not only in retinoblastomas but has been described in a wide variety of human neoplasms. The retinoblastoma gene encodes a nuclear phosphoprotein that in its hypophosphorylated state plays an important role in regulating the cell cycle, thus preventing from tumour formation. Expression of retinoblastoma gene protein product (pRB) was investigated in 118 formalin-fixed, paraffin-embedded cervical tissues by immunohistochemistry using commercially available antibody directed against RB protein. Ten normal ectocervical epithelium, 16 cervical intraepithelial neoplasia (CIN) I, 13 CIN II, 14 CIN III, 53 invasive squamous cell carcinoma, 11 adenocarcinoma and 1 small cell carcinoma were selected for this study. The proportions of pRB-positive cells as well as the extent of pRB expression in ectocervical squamous epithelium were assessed and compared among the lesions. The pRB expression was observed in 100% of normal ectocervical epithelium (n=10), 100% of CIN lesions (n=43) and 98.5% of invasive carcinoma of the uterine cervix (n=65) and were statistically significant when CIN or CIN/invasive were compared to normal cases (P < 0.01, P < 0.05 respectively). While in invasive squamous cell carcinoma (SCC), 81.8% (9/11) pRB-positive cells were found in much higher percentages in well differentiated SCC compared to 64.3% (18/28) of moderately differentiated cases and only 7.1% (1/14) of poorly differentiated SCC (P < 0.01, respectively). The results of this study suggest that loss of RB protein expression is rare in carcinoma of the uterine cervix and this protein may be important in the pathogenesis of cervical carcinoma.