563
ASSESSMENT OF ENDOMETRIAL PROLIFERATION WITH MONOCLONAL ANTIBODY KI-S2 IN ANTIPROGESTIN-TREATED MACAQUES.
Slayden, Ov1, Nayak, Nihar1, Heidebrecht, Hans-Jurgen2, Brenner, Robert 1, 1 2
ABSTRACT- Ki-S2 is a new monoclonal antibody developed against a 100 kD nuclear protein (p100) expressed only in S, G2 and M phases of the cell cycle. Although the Ki-67 antigen is a commonly used marker for proliferating cells, many Ki-67 positive cells never progress to mitosis (Heidebrecht et al., Blood : 90:266-233). Therefore the Ki-67 index overestimates the number of mitotic cells in a histological section. For example, we found that antiprogestin (AP) treatment dramatically inhibited the effects of estradiol (E) on endometrial glandular mitosis, but only minimally reduced the Ki-67 index (Slayden et al. Human Reprod. 13:269-277,1998). In the current work we evaluated the Ki-S2 antibody as an immunocytochemical reagent and a marker of proliferation in rhesus macaque endometria. We compared glandular mitotic indices with immunostaining by Ki-67 and Ki-S2 in endometria collected from spayed macaques treated with either E alone or E plus the antiprogestin ZK 137 316 (ZK; n=3/group). The mitotic index, expressed as the mean (+SE) mitotic cell number/1000 epithelial cells was: E alone, 6.25+ 0.6; E+ ZK, 0.3+0.25. The mean (+ SE) percent Ki-67 positive cells was E alone, 25+ 2.8%; E + ZK, 21.2+7.8 %. The mean (+ SE) percent Ki-S2 positive cells was E alone, 10.1+0.9%; E+ZK 1.3+1%. Clearly, Ki-S2 staining closely parallels the number of endometrial cells that enter mitosis, and unlike Ki-67, reflects the inhibitory action of APs on E-dependent growth. In sum, the Ki-S2 antibody is a new immunocytochemical tool that will greatly facilitate the study of cell proliferation in reproductive tissues. Supported by HD39363 (ODS), DMAD 17-996-C-6096 (RMB), and RR-00163.
KEY WORDS: Ki-S2, cell proliferation, macaque, endometrium