MIB-1 IMMUNOSTAINING IN CERVICAL INTRAEPITHELIAL NEOPLASIA - PROGNOSTIC-SIGNIFICANCE IN MILD AND MODERATE LESIONS

Objective: MIB 1 is a new monoclonal antibody which recognizes nuclei of proliferating cells throughout the cell cycle except during the G(0 ) and early G(1) phases. In the present study we analyzed the MIB 1 im munostaining as an index of cellular proliferation in cervical intraep ithelial neoplasia (GIN) and microinvasive carcinoma, with the aim to identify a relationship with the degree of dysplastic lesion and the r isk of neoplastic progression. A correlation between the MIB 1 index a nd human papillomavirus (HPV) DNA presence was also investigated. Meth ods: Cervical bioptic samples were consecutively obtained from 86 wome n who attended our Colposcopic Service from January 1993 to June 1994, because of abnormal pap smears suspicious for cervical dysplasia and/ or HPV infection. On histologic evaluation, 41 women had CIN, 23 cervi cal condyloma, and 22 squamous metaplasia. Ten patients with microinva sive squamous cervical carcinoma, matched for age and demographic char acteristics, were selected from our series of cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor cellul ar proliferation was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-pr ocessed formalin-fixed paraffin-embedded tissue. Positive staining was expressed as the percentage of positive cells per 10(3) counted dyspl astic cells for each case. Results: A progressive significant increase in positive MIB 1 immunostaining was observed from squamous metaplasi a to microinvasive carcinoma throughout the CIN lesions (p < 0.001). C onsidering only CINs, the MIB 1 index showed a significant increase wi th respect to CIN degrees (p < 0.001); no correlation was found betwee n MIB 1 immunostaining and HPV infection, and lesion size. By analyzin g the MIB 1 index with respect to CIN outcome in mild and moderate dys plasias, regressive lesions had lower values of MIB 1 immunostaining, while persistent and progressive lesions presented significantly highe r positivity (p < 0.001). Conclusions: Our data demonstrated: (1) that positive MIB 1 immunostaining increased progressively from squamous m etaplasia to CIN and microinvasive carcinoma, suggesting that neoplast ic transformation is associated with a dysfunctional proliferation of cervical epithelium; (3) that there was a significant correlation betw een the MIB 1 index and CIN degree but not with respect to HPV DNA pre sence, and (3) that MIB 1 immunostaining might be useful for a clinica l evaluation of mild and moderate dysplastic lesions. However, a much larger study needs to be done over a longer period of time to truly de termine the value of the technique in prognostically predicting which lesions might or might not regress.