IMMUNE RECOGNITION OF ENDOMETRIAL TUMOR-ANTIGENS INDUCED BY MULTIPARITY

Objective. The risk of developing endometrial cancer is reduced with i ncreasing parity. The purpose of this study was to investigate the pos sibility that maternal immunization against fetal antigens might be el icited during pregnancy and, if so, to characterize antigens reactive with this immune response. Methods. Sera were obtained from nulliparou s (n = 9) and multiparous women (n = 14). Cellular proteins were isola ted 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 f rom KLE tumor cells by immunoaffinity columns. Three commonly recogniz ed proteins were identified, separated, and processed for internal mic rosequencing.Results. Sera from multiparous women, used as primary ant ibodies, 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), e pidermal fatty acid binding protein (18 kDa), and keratin 10 (54 kDa). Nulliparous women failed to recognize these antigens. Conclusion. The se findings suggest that certain antigens expressed by the fetus and/o r the placenta immunize women during pregnancy. This immune response m ay protect these women from developing endometrial cancer and explain epidemiologic findings. Future studies will explore the utility of the se reexpressed fetal antigens as possible targets for active immunothe rapy. (C) 1998 Academic Press.