bcl-2 protein expression in cervical intraepithelial neoplasia: No evidence of a prognostic significance in mild and moderate lesions

Background: The bcl-2 proto-oncogene codes for a protein which appears to b lock apoptosis. In our study, we examined bcl-2 protein expression in cervi cal squamous metaplasia, cervical intraepithelial neoplasia (CIN) and micro invasive squamous carcinoma with the aim of identifying a relationship betw een bcl-2 protein expression and neoplastic development and progression. Ma terials and Methods: Cervical bioptic samples were obtained fi om 86 white women, selected consecutively from our Colposcopic Service from January 199 3 to June 1994, because of abnormal pap- smear suspicious for cervical dysp lasia and/or human papilloma virus (HPV) infection. Upon histologic evaluat ion, 41 women had GIN, 23 cervical condyloma, and 22 squamous metaplasia. T en patients with microinvasive squamous carcinoma, matched for age and demo graphic characteristics, were selected from our series of invasive cervical carcinomas and immunohistochemically analyzed. The expression of primary t umor bcl-2 protein was immunohistochemically evaluated by antihuman bcl-2 m onoclonal antibody (diluted 1:100, Dako, Copenhagen, Denmark) on formalin-f ixed paraffin-embedded tissue. Positive staining was expressed as a percent age of positive cells pei 1000 counted dysplastic cells for each case. Resu lts: Bcl-2 immunostaining was found in all the 22 squamous metaplasias, lim ited to the basal layer: Nineteen of the 41 CINs (46%) were bcl-2 immunorea ctive, and 2 of the 10 microinvasive carcinomas (20%). By analysing CIN les ions, the bcl-2 protein showed a striking increase in the tale of positivit y with increasing severity of GIN; the bcl-2 protein expression in CINs III was significantly higher than for CINs I, CINs II or microinvasive carcino mas (P=0.03, P=0.02, and P=0.03 respectively). No relationship was observed between bcl-2 immunostaining and HPV infection. bcl-2 protein expression w as not useful for predicting CIN I and II evolution, although the rate of p ersistence/progression was higher in bcl-2 positive dysplasias (7 of 9 case s, 78%) than in negative ones (13 of 21 cases, 62%) (p = 0.88). Conclusions : Based on these results, it seems possible that the increase in bcl-2 expr ession in higher grade of CINs implies an increasing protection against pro grammed cell death, bnl also the induction of genetic instability in dyspla stic epithelial cells and a greater capacity to evolve into invasive carcin oma.