Phenotypic Alteration of Carbohydrate Antigens in Gynecological Malignancy

Two monoclonal antibodies termed MSN-1 and MRG-1 were raised against endometrial cancer cell line SNG-II and ovarian mucinous cystadenocarcinoma cell line RMUG-L, respectively, and were found to recognize carbohydrate antigens, Lewis b (Le^b) and blood-group A type 3 structures, respectively. Using these monoclonal antibodies, we examined phenotypic alterations of the corresponding carbohydrate antigens in gynecological malignancies including uterine cervical and endometrial cancers. Additionally, since galactosyltransferase associated with tumor (GAT), which is derived from cellular galactosyltransferase (GalT), is frequently elevated specifically in the sera of patients with ovarian cancer, the localization of GalT and GAT was investigated in malignant ovarian tumors. Light-microscopically, MSN-1 gave a positive reaction in more than 90% of the cases of endometrial cancers. The suborganellar localizations of MSN-1-reactive antigen in the cancer cells were almost all in the cisternae of the Golgi, while the normal endometrial glandular cells showed a few positive signals in the trans-Golgi only. Using MRG-1 we investigated uterine cervical squamous epithelial lesions as well as their normal counterparts. Normal squamous epithelium showed a strong positive reaction exclusively along the cell surface. MRG-1-binding sites in squamous cell carcinoma were not only along the cell surface but also in the cytoplasmic space where they resided on vesicular structures, as observed at the electron microscopic level. To detect the galactosyltransferase, we employed two monoclonal antibodies, Mab8628 and Mab8513. Mab8628 strongly stained intracytoplasmic structures in ovarian cancer cells that coincided with the trans-Golgi, as observed with the electron microscope. When Mab8513, which can recognize GAT more specifically than Mab8628, was applied to endometrial cancer and normal cells, an increase in the positive signals was found in cancer cells. These histochemical analyses demonstrated that the localization and/or amount of complex carbohydrates as well as glycosyltransferase is altered between cancer cells and their normal counterparts.