CORRELATION OF LESION GRADE IN CERVICAL NEOPLASIA WITH CELL-PROLIFERATION AND APOPTOSIS

In order to understand better the mechanisms underlying the developmen t of cervical neoplasia, we examined the indices of cellular prolifera tion and apoptosis in cervical neoplasia. Archival cervical tissue sam ples from normal cervix, low-grade squamous intra-epithelial lesions ( LSIL), high-grade squamous intra-epithelial lesions (HSIL), and squamo us cell carcinomas were evaluated for the expression of nuclear antige n Ki-67 and chromatin cleavage, a hallmark of apoptosis. Five-micromet er sections from each case were immunohistochemically stained using MI B-1 mouse monoclonal antibody, and Ki-67 index was defined as the numb er of positively labeled cells per 100 cells. Apoptosis was determined by in situ end-labelling of DNA strand breaks induced by terminal deo xynucleotidyl transferase (TdT) and was expressed as apoptotic index ( AI = [sum of apoptotic bodies/total epithelial nuclei] x 100). To comp ensate for the effect of proliferative fraction on AT, corrected apopt otic index (CAI = [AI/Ki-67 index] x 100) was calculated. Both the Ki- 67 index and AI significantly increased (P < 0.001, both) as the grade of cervical neoplasia increased. Corrected AI also significantly incr eased (P < 0.001) with lesion grade. These data suggest that the progr ession of neoplasia in the uterine cervix is accompanied by increased cellular deletion as well as cellular proliferation. The significant c orrelation of corrected AT with lesion grade suggests that apoptosis m ay have an independent role in the development of preinvasive and inva sive cervical lesion.