Subcellular localization of MUC1 recognized by a monoclonal antibody MY.1E12 correlates with postsurgical prognosis in differentiated-type gastric carcinomas of stage II and III

Abstract

Because of the complex nature of the diverse histologic grade in gastric carcinomas a useful biomarker should be provided to scale the aggressiveness of the disease and to determine surgical strategy, especially for advanced carcinomas. Our previous study of MUC1 in gallbladder carcinoma using mAb MY.1E12 has revealed the stromal localization of MUC1 adjacent to the carcinoma was correlated with poor prognosis. In gastric carcinoma the biological significance of the localization of MUC1 recognized by mAb MY.1E12 has not been fully investigated. We performed immunohistochemical analysis to determine the correlations with the localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) and clinicopathological findings. A total of 91 consecutive patients with stage II, IIIA or IIIB gastric carcinoma after curative resection were reviewed retrospectively. The localization of MY.1E12-MUC1 was classified as negative, apical, cytoplasmic or stromal type based on the predominant subcellular localization. Immunostaining of MY.1E12-MUC1 was recognized in 84% of the 55 cases of differentiated-type carcinoma and in 53% of the 36 cases of undifferentiated-type carcinoma (P<0.01). In differentiated-type carcinoma, the proportion of stromal-type dominant localization of MY.1E12-MUC1 was increased at the deepest invading sites. Postsurgical liver metastasis was seen in 11 (30%) of 37 cases showing stromal or cytoplasmic-type localization-dominant group and in 1 (6%) of 18 cases showing apical-type localization-dominant group or negative staining group (P<0.05). The postsurgical survival was significantly poorer in the former group than in the latter (P=0.004). In differentiated-type gastric carcinoma, the presence of the cytoplasmic- or stromal-type localization of MY.1E12-MUC1 at the deepest invading sites correlates with aggressiveness of the disease, such as the tendency to form liver metastasis. This phenotype may serve as a unique biological feature associated with the malignant behavior of differentiated-type gastric carcinomas.