BUB1 Immunolocalization in Breast Carcinoma: Its Nuclear Localization as a Potent Prognostic Factor of the Patients

Mitotic checkpoint is a fundamental mechanism involved in fidelity mitotic chromosome segregation, and its alteration results in progression of human malignancies. In this study, we examined expression profiles of seven mitotic checkpoint genes in 20 breast carcinomas using microarray analysis. Results demonstrated that BUB1 expression level was closely correlated with the proliferation activity evaluated by Ki-67 labeling index (LI) of individual cases. Therefore, we further immunolocalized BUB1 in 104 breast carcinoma tissues in order to evaluate its clinicopathological significance. BUB1 immunoreactivity was detected in the nucleus and/or cytoplasm of carcinoma cells, and nuclear and cytoplasmic BUB1 status were positive in 40% and 58% of the cases examined, respectively. In particular, nuclear BUB1 status was significantly associated with stage, pathological tumor factors, lymph node metastasis, distant metastasis, histological grade, and Ki-67 LI, but cytoplasmic BUB1 status was not significantly associated with any of the parameters examined. Subsequent multivariate analysis revealed that nuclear BUB1 status turned out an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients examined. These results all indicated that BUB1 played important roles in the proliferation and/or progression of the breast carcinoma, and nuclear BUB1 immunohistochemical status is also considered a potent prognostic factor in human breast cancer patients.