子宮体癌の発生に伴う複合糖質発現異常に関する基礎的研究とその臨床へのフィードバック (<シンポジウム>子宮体癌の発生と発育)

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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 α1-2FT, α1-3FT and α1-4FT were higher in endometrial cancer than in normal endometrium. Furthermore, we determined the activity of α1-2FT and α1-4FT 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 recongnized by MSN-1. There was a positive corelation 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 α1-4FT activity between these two groups. Apparently, SNG-W did not express much MSN-1 reactivity because these cells had a low activity of α1-4FT. These results suggest that the promotion of glycosyltransferase activity during the neoplasia of endometrial cells is strongly concerned with the abnormal expression of carbohydrate side chains. 3. Usefulness in clinical application We evaluated the relationship between the stage of cancer and reactivity to MSN-1, and that between the reactivity of moderately differentiated endometrial cancer to MSN-1 and a 5-year survival rate. Endometrial cancer with a poor prognosis tended to react poorly to MSN-1, suggesting the possibility that the reactivity to MSN-1 is useful as a new prognostic factor. A study of endometrial hyperplasia revealed that the reactivity to MSN-1 was high in the high-risk groups (individuals diagnosed as endometrial cancer later). This suggested that the analysis of the expression of the antigen recognized by MSN-1 is useful in selecting the high risk group out of patients with endometrial hyperplasia. Furthermore, we consider that examination for abnormal expression of glycoconjugate associated with neoplasia of endometrial cells is useful in developing a new diagnostic method, for example our endometrial cell enzymeimmunoassay (CmC-EIA) with MSN-1 and will be helpful in developing therapeutic approaches, such as missile therapy with
社団法人日本産科婦人科学会の論文
1993-08-01

子宮体癌の発生に伴う複合糖質発現異常に関する基礎的研究とその臨床へのフィードバック (<シンポジウム>子宮体癌の発生と発育)

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