[Abnormal expression of glycoconjugate associated with the development of endometrial cancer: a basic study and its usefulness in clinical application]

Abstract

We studied the abnormal expression of a glycoconjugate that appears in the process of neoplasia of endometrial cells and tried to shed light on the mechanism of their expression. Furthermore, we evaluated the effectiveness of its use in clinical application. 1. Investigation of abnormal expression of glycoconjugate We performed an immunohistochemical study on the expression of blood group-related carbohydrate antigens in endometrial cells, and found that carbohydrate side chains with galactose and fucose at their terminals were increased in association with neoplastic transformation. Using anti-endometrial cancer monoclonal antibody MSN-1, we showed that abnormal expression had already been induced in endometrial hyperplasia and increased as the lesions grew worse. A biochemical study of glycolipids showed that sulfatide (one of the sulfoglycolipids) was produced in endometrial cells, and that it varied in amount depending on the menstrual cycle, and was increased in endometrial cancer cells. Hydroxylation, which is recognized in cells in the fetal period, was seen in the ceramide region of these glycolipids. 2. Shedding light on the mechanism of the abnormal expression of glycoconjugate We examined normal and neoplastic endometrial cells for differences in the level of galactosyltransferase (GT) and fucosyltransferase (FT). Immunohistochemical staining with monoclonal antibody 8628 (an anti-GT antibody) gave the following results: GT gave a fine granular staining confined to the cytoplasma between the nucleus and glandular lumen in 70% of the cares of normal endometrium: In contrast, GT was found extensively in either a coarse granular state or spread diffusely throughout the cytoplasm in about 70% of the endometrial cancer specimens. We were also able to determine FT activity in normal and cancerous endometrial tissues by our newly developed method. The levels of alpha1-2FT, alpha 1-3FT and alpha 1-4FT were higher in endometrial cancer than in normal endometrium. Furthermore, we determined the activity of alpha 1-2FT and alpha 1-4FT in both endometrial cancer tissue and cell cultures derived from gynecological cancer, and examined the relationship between their activity levels and expression of the antigen recognized by MSN-1. There was a positive correlation between them. SNG-II cells were classified in terms of their reactivity to MSN-1 into two groups: 1) SNG-S, which was strongly reactive to MSN-1, and 2) SNG-W, which was weakly reactive to the antibody. FT activity was compared between these two cell groups. There was a marked difference in alpha 1-4FT activity between these two groups.(ABSTRACT TRUNCATED AT 400 WORDS)