title: BUB1 immunolocalization in breast carcinoma: its nuclear localization as a potent prognostic factor of the patients.
abstract: 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.
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, 980-8575, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shibahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Ebata
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases