Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: Serous and mucinous tumors exhibit distinctive patterns of expression

Abstract

Expression of blood group-related carbohydrate antigens was examined in frozen sections from a series of ovarian carcinomas of different histological types using an indirect immunoperoxidase technique. Antigenic specificities belonging to the O(H) and Lewis blood group families (H-1, H-2, Le a , sLe a , Le x , sLe x , Le b and Le y ) or the mucin-core family (Tn, sTn and TF) were studied. A distinct difference in antigen expression between mucinous and other ovarian carcinomas (serous and endometrioid) was observed. Specifically, mucinous tumors tended to express sTn, Le a and sLe a strongly and homogeneously, whereas serous and endometrioid tumors rarely expressed these specificities and, in contrast, expressed Le y and H type 2 antigen strongly. When expressed in serous tumors, sTn was usually distributed in a heterogeneous pattern, whereas sTn expression in mucinous tumors was much more homogeneous. The distribution of Le y in serous tumors was noticeably homogeneous. H-1, Le x , sLe x, , Le b , TF and Tn specificities were rarely expressed in any type of ovarian carcinoma. Our results provide further support for the different histogenesis of mucinous and non-mucinous tumors and indicate alternative differentiation pathways for the 3 pathological subtypes of ovarian tumor. They also provide the basis for the choice of carbohydrate antigens for active and passive immunotherapy of ovarian carcinomas. Int.

Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial

“…Whether a single component vaccine, capable of inducing only an antibody response, would be expected to be effective is unknown. The greatest impediment to a successful outcome is probably the heterogeneity of antigen expression within tumor lesions, although the expression of Le y in ovarian tumors, as judged by immunohistology, is relatively uniform (Federici et al, 1999), particularly in comparison with other carbohydrate specificities.…”

“…For instance, although Le y is highly expressed on the majority of serous and endometrioid carcinomas, it is poorly expressed on mucinous tumors. Correspondingly, STn and Tn epitopes are well expressed on mucinous tumors but poorly synthesized by serous tumors (Federici et al, 1999). Some normal tissues, e.g., epithelial cells and their secretions in the esophagus, stomach, proximal small intestine, and some acinar cells of the pancreas, also express Le y Hellström et al, 1990).…”

“…Identifying carbohydrate epitopes that are overexpressed in ovarian cancer cells has opened up the possibility of using these structures as vaccines. Among possible targets are Lewis y (Le y ), globo H, STn, Tn, and T-F, which are expressed on the glycolipids, glycoproteins, and mucins synthesized by ovarian cancer cells (Federici et al, 1999;Zhang et al, 1997). Some of these specificities are carried on the MUC-1 mucin, which serves as a target antigen in its own right.…”

“…Some of these specificities are carried on the MUC-1 mucin, which serves as a target antigen in its own right. To some extent, the pattern of expression of these antigens varies according to the pathological subtype of the tumor (Federici et al, 1999). For instance, although Le y is highly expressed on the majority of serous and endometrioid carcinomas, it is poorly expressed on mucinous tumors.…”

“…Miles et al (1996) have pioneered the use of an sTn conjugate as a vaccine. On the basis of the high expression of Le y in ovarian cancer (Federici et al, 1999) and the results of a preclinical study in mice demonstrating the superior immunogenicity of a Le y oligosaccharide-KLH conjugate (Kudryashov et al, 1997), we initiated a trial of this vaccine in patients with ovarian cancer.…”