The clinicopathological and prognostic significance of MUC-1 expression in Japanese gastric carcinomas: an immunohistochemical study of tissue microarrays.

BACKGROUND: MUC-1 is synthesized as a single polypeptide that then undergoes proteolytic cleavage, and is associated with the epidermal growth factor receptor tyrosine kinases. In malignancies, MUC-1 may function as an anti-adhesion molecule, but can also promote adhesion and presumably metastasis.

MATERIALS AND METHODS: Expression of MUC-1, -2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas (n = 237) and adjacent non-cancerous mucosa specimens (n = 89) by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients.

RESULTS: MUC-1 was found to be highly expressed in gastric carcinomas in comparison with noncancerous mucosa (p < 0.05) and positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, UICC staging and MUC-4 expression (p < 0.05), but not with age, tumor size, MUC-2 or MUC-5AC expression (p > 0.05). Intestinal-type carcinomas showed more MUC-1 expression than their diffuse-type counterparts (p < 0.05). Kaplan-Meier analysis indicated that the cumulative survival rate of patients with no MUC-1 expression was significantly higher than those with weak, moderate or strong expression in gastric carcinomas (p < 0.05), but no difference was observed when tumors were stratified according to the depth of invasion (p > 0.05). Cox's analysis showed three independent prognostic factors, depth of invasion, lymphatic invasion and venous invasion, to affect the relationship between MUC-1 expression and prognosis.

CONCLUSION: Up-regulation of MUC-1 expression may be involved in pathogenesis, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behavior of gastric carcinoma. MUC-1 expression was found to be a prognostic factor for gastric carcinoma patients, albeit not independent of parameters of invasion.