ABH and related histo-blood group antigens in normal & malignant human endometrium in relation to genetic and hormonal factors.

Abstract

Recent immunohistochemical studies have shown that endometrial carcinomas are characterized by changes in glycosylation involving histo-blood group antigens. These carbohydrate determinants are present not only on erythrocytes but are also expressed by epithelial cells. Their expression herein has been shown to be related to the genetic status of the individual in terms of the ABO, Lewis and ABH-secretor type. Moreover, they show changes in expression relating to development, tissue-type, differentiation, cell-motility and malignancy. Meanwhile, most studies performed on endometrial tissue have not considered duly that histo-blood group antigen expression herein may be influenced by genetic and hormonal factors. Using immunohistochemistry and MABs with specificity to ABH- and related histo-blood group antigens with different peripheral core structures we have studied the expression of these carbohydrates in the human endometrium in relation to genetic and hormonal factors. The present paper presents a summary and a discussion of present knowledge on expression of histo-blood group antigens in the normal and malignant human endometrium. In addition, the possible regulatory mechanisms that control their expression in the endometrium are discussed. The histo-blood group phenotype of normal endometrial epithelial cells show great complexity. Variations in expression are related to the genetic status, i.e., the ABO, Lewis and ABH-secretor status. However, our findings suggest that the regulation of Lewis antigen expression in the endometrium differs from that in erythrocytes. Moreover, expression of histo-blood group and related carbohydrates varies with layer, mucosal histology, cell-type and hormone levels in serum. In glands in the functionalis and basalis, the histo-blood group phenotype is characterized by a predominant expression of sialylated types 2 and 3 chains. Expression of ABH determinants is, in general, low. However, the expression of fucosylated and terminal ABH determinants vary with the menstrual cycle, degree of proliferation and hormone levels in serum. The secretory phenotype is characterized by an increased expression of type-1 chain antigens, and by expression of sialylated chains as S-Tn, MS-Le(a), DS-Lac. A/B transferase protein expression was found to correlate with E2 levels in serum. These findings in conjunction with studies of glycosyltransferase activity in murine endometrial cell strongly suggest that the endometrial epithelial cell histo-blood group phenotype is also modulated by the ovarian hormones. The histo-blood group phenotype of endometrial carcinomas and precursor lesions is also influenced by the ABO, Lewis and secretor-status. Except for loss of A/B transferases and A/B antigens, which appear to be a late event, the changes are demonstrable also in preneoplastic endometrial cells. The malignant phenotype is characterized by an increased expression of type-1 chain carbohydrates. ABH-secretors express H and Le(b) antigens in addition to Le(a) and S-Le(a) antigens, whereas ABH-non-secretors express Le(a), and S-Le(a) determinants mainly. Moreover, endometrial carcinomas express Tn antigen, and sialylated carbohydrates, which are expressed in luteal phases of the normal endometrium, i.e., S-Tn, DS-Lac, and MS-Le(a) antigens. Thus the histo-blood group phenotype of endometrial carcinoma cells in many ways shows a resemblance to that of secretory endometria. The relation between expression of T, S-T and A/B transferase protein and E2 levels in serum was maintained in endometrial carcinomas. Expression of H, Le(b), LeX, S-LeX, and LeY was related to the tumour grade, whereas only expression of H determinants was related to the FIGO stage. In accord, recent studies have suggested that expression of H and Le(b) antigens in endometrial carcinomas may be correlated with prognosis. An increased activity of alpha 1-2 and alpha 1-3/4 fucosyltransferases has recently been demonstrated in endometrial carci