PROGRESSING IMBALANCE BETWEEN PROLIFERATION AND APOPTOSIS WITH INCREASING SEVERITY OF CERVICAL INTRAEPITHELIAL NEOPLASIA

The equilibrium between cell proliferation and protection against apop tosis was studied immunohistochemically using monoclonal antibodies ag ainst Ki-67-Ag and bcl-2, respectively, in consecutive sections from n ormal and metaplastic cervical epithelia and cervical intraepithelial neoplasia (GIN) lesions and cervical carcinomas. A high percentage of Ki-67-Ag positive cells was seen in the parabasal cells of normal ecto cervical and mature squamous metaplastic epithelium, although the basa l cells were virtually negative. In preneoplastic lesions, however, th e basal cells showed high proliferative activity and an increasing fre quency of Ki-67-Ag positive cells was observed in the higher epithelia l layers with increasing severity of CIN. In squamous cell carcinomas, variable numbers of Ki-67-Ag positive cells were observed and in aden ocarcinomas expression increased with the degree of anaplasia. bcl-2 e xpression was observed only in the basal cells of normal endo-and ecto cervix including reserve cells. With increasing severity of CIN, stain ing intensity and number of bcl-2 positive cells gradually increased. Five of eight squamous cell carcinomas were variably positive. All fiv e adenocarcinomas showed extensive bcl-2 expression. Increased express ion of both Ki-67-Ag and bcl-2 with increasing severity of CIN indicat es an increasing imbalance between cell proliferation and protection f rom apoptosis. It is therefore proposed that an increasing proliferati ve fraction combined with a higher number of cells protected from apop totic cell death contributes to progression of CIN. This phenotype may identify premalignant lesions with the potential to transform to cerv ical cancer.