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, Lea, sLea, Lex, sLex, Leb and Ley) 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, Lea and sLea strongly and homogeneously, whereas serous and endometrioid tumors rarely expressed these specificities and, in contrast, expressed Ley 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 Ley in serous tumors was noticeably homogeneous. H‐1, Lex, sLex,, Leb , 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. J. Cancer 81:193–198, 1999. © 1999 Wiley‐Liss, Inc.

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

“…The role of mucins as STn carriers in mucinous cancers has recently been confirmed using the Proximity Ligation Assay [53]. Squamous cancer cells are mainly and intensively stained in the cytoplasm and sometimes on the cell membrane [23,52,54]. This supports the idea that STn antigen is carried by a diversity of glycoproteins differently expressed and/or processed according to the cell type.…”

“…Mucinous cancer cells are stained on the whole cell membrane, focally in the cytoplasm (perinuclear area, presumably Golgi) and sometimes in extracellular compartments [19,39,52]. This indicates that STn is carried by both membrane bound and secreted glycoproteins such as mucins.…”

The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

“…Previously, glycan epitopes expressed by epithelial ovarian cancer cells were mostly studied by immunohistochemical analyses using monoclonal antibodies detecting Lewis-type structures (Le a/x , Le y/b , Sialyl-Le a (sLe a )), Tn and STn and monoclonal antibodies against blood group antigens A,B and O/H [36, 48, 49]. In these studies, the high expression of the Le y epitope was described for serous ovarian tumors, however, mucinous ovarian tumors were shown to react strongly to sLe a antibody.…”

Pilot Study of a Heptavalent Vaccine-Keyhole Limpet Hemocyanin Conjugate plus QS21 in Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

“…These include carbohydrate epitopes, such as GM2, Globo-H, Lewis Y, sialyl Tn (STn), Tn, Thompson Friedreich antigen (TF), and mucin 1 (MUC1; refs. [6][7][8][9]. For the production of antibodies against defined cell surface antigens such as these, the best approach has been described to include chemical conjugation of the antigen to a highly immunogenic carrier protein plus the use of a potent immunologic adjuvant.…”