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Expression of MUC1 Mucins in the Subserosal Layer Correlates with Postsurgical Prognosis of Pathological Tumor Stage 2 Carcinoma of the Gallbladder¹

Departments of Gastrointestinal Surgery [T. K., N. K., K. F., T. T.] and Gastroenterology [J. S., T. A., M. K., N. T.], Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575; Department of Cancer Biology and Molecular Immunology, Faculty of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 [T. I., N. M.]; Second Department of Surgery, Nagasaki Central National Hospital, Nagasaki 856-0835 [M. F.]; Department of Pharmaceutical Research, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc., Tokyo 174-8555 [T. U.], Japan

The overall outcome of pT₂ gallbladder carcinoma has not been favorable. Postsurgical recurrence at distant sites occurs in some cases, although the carcinoma was limited to the gallbladder wall. A high level expression of MUC1 mucins with sialylated carbohydrates (sialylated MUC1 mucins) is correlated with poor survival in intrahepatic bile duct carcinoma. In the present study, immunohistochemistry was performed to determine the expression level of sialylated MUC1 mucins, detected by a monoclonal antibody, MY.1E12, in 31 cases of pT₂ gallbladder carcinoma on which curative resections had been performed and to determine the correlation of the expression level of MY.1E12-reactive-MUC1 mucin with mode of recurrence and postsurgical survival. Immunostainings of the MUC1 mucin were recognized in different types of noncancerous pathological epithelia of the gallbladder except for intestinal metaplasia and cancerous epithelia. Immunohistochemical localization was classified into apical, cytoplasmic, and stromal types based on the predominant cellular distribution of MY.1E12-reactive-MUC1 mucin. In 31 cases of pT₂ carcinoma, the localization was apical type in 64%, cytoplasmic type in 71%, and stromal type in 48% of the cases at the deepest invading sites in the subserosal layer. Distant recurrences, i.e., peritoneal dissemination in 8 patients and liver metastasis in 3 patients, were seen in 8 (53%) of 15 cases of pT₂ carcinoma that had 10% of the cancerous epithelia showing stromal localization of the MUC1 mucin at the deepest invading sites and in 2 (12%) of 16 cases that had <10% of those showing the stromal localization. The postsurgical survival outcome was significantly poorer in the former than in the latter (P = 0.044). In pT₂ gallbladder carcinoma, the presence of MY.1E12-reactive-MUC1 mucin in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT₂ gallbladder carcinoma.

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