Immune Recognition of Endometrial Tumor Antigens Induced by Multiparity

Abstract

The risk of developing endometrial cancer is reduced with increasing parity. The purpose of this study was to investigate the possibility that maternal immunization against fetal antigens might be elicited during pregnancy and, if so, to characterize antigens reactive with this immune response. Sera were obtained from nulliparous (n = 9) and multiparous women (n = 14). Cellular proteins were isolated from normal endometrium and cultured cells from early (HEC-1A) and late (KLE and RL95-2) stage endometrial cancers. These were separated by SDS-PAGE and those proteins reactive with each individual's serum were assessed by Western immunoblot. Reactive proteins were isolated from KLE tumor cells by immunoaffinity columns. Three commonly recognized proteins were identified, separated, and processed for internal microsequencing. Sera from multiparous women, used as primary antibodies, recognized multiple bands on endometrial tumors, ranging from 10 to 120 kDa. Several antigens were commonly recognized by the sera of multiparous women. The three commonly recognized proteins, normally expressed by fetal tissues, were identified as cystatin A (10 kDa), epidermal fatty acid binding protein (18 kDa), and keratin 10 (54 kDa). Nulliparous women failed to recognize these antigens. These findings suggest that certain antigens expressed by the fetus and/or the placenta immunize women during pregnancy. This immune response may protect these women from developing endometrial cancer and explain epidemiologic findings. Future studies will explore the utility of these reexpressed fetal antigens as possible targets for active immunotherapy.