Alterations in Gastric Mucin With Malignant Transformation: Novel Pathway for Mucin Synthesis

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Abstract
Background : Mucins are high-molecular-weight glycoproteins produced by both normal and cancer cells. However, in cancer cells, abnormal mucins are synthesized and potentially can be used as markers for the development and progression of certain malignancies. In a previous study, we reported the production of a new monoclonal antibody directed against a mucin antigen termed F1α, an O -linked oligosaccharide similar to sialyl Tn and Thomsen-Friedenreich (T) antigens, that has not been previously detected in human cancers. F1α is expressed in a high percentage (80.2%; 89/111) of gastric cancers. Purpose : In the present study, we compared the expression of F1α with that of sialyl Tn and T antigens in human gastric cancer tissues to determine how differences in the expression of these cancer-associated antigens correlated with the biological properties of cancer cells. Methods : A total of 141 cases of gastric cancer were studied. Sections of formalin-fixed, paraffinembedded tissue were immunostained for F1α, sialyl Tn, and T antigens. The relationship between the expression of these antigens and the patient's clinicopathologic characteristics was studied. The chi-square test (two-sided) was used for statistical analyses. Results : F1α was expressed in a high percentage of the cases of early to advanced cancers, irrespective of the degree of malignant progression. The rate of expression of sialyl Tn antigen in early carcinoma was low, but it increased significantlyl as depth of invasion increased ( P <.05) and was significantly higher in patients with hepatic or lymph node metastasis than in those without such metastasis ( P <.01). Expression of T antigen significantly increased with depth of invasion ( P <.01) and was significantly higher in patients with hepatic metastasis ( P <.05), lymph node metastasis ( P <.05), or peritoneal dissemination ( P <.01) than in those without such metastasis or dissemination. In consecutive sections of the same specimen, the sites of staining for Flα and sialyl Tn antigens seldom coincided. In many cases, Flα staining was predominant, but the sialyl Tn-dominant region tended to increase as gastric cancer progressed. Regions of T-antigen staining were usually circumscribed by those of Flα staining. Conclusion : Our findings indicate that the expression of Flα begins almost at the same time as does carcinogenesis in gastric epithelial cells. Moreover, in association with progression of gastric carcinoma, synthetic pathways for sialyl Tn antigen and T antigen probably are activated independently. [J Natl Cancer Inst 87: 441–446, 1995]

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