title: Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor.
abstract: Cyclin B1 is translocated to the nucleus from the cytoplasm, and plays an essential role in cell proliferation through promotion of mitosis. Although overexpression of cyclin B1 was previously reported in breast carcinomas, the biological significance of the intracellular localization of cyclin B1 remains unclear. Therefore, in this study, we examined cyclin B1 immunoreactivity in 109 breast carcinomas, according to the intracellular localization, that is, nucleus, cytoplasm or total (nucleus or cytoplasm). Total cyclin B1 was detected in carcinoma cells in 42% of breast carcinomas examined, whereas nuclear and cytoplasmic cyclin B1 were positive in 17 and 35% of the cases, respectively. Total or cytoplasmic cyclin B1 were positively associated with histological grade, mitosis, Ki-67, p53, c-myc or 14-3-3sigma, and inversely correlated with estrogen or progesterone receptor. Nuclear cyclin B1 was significantly associated with tumor size, lymph node metastasis, histological grade, mitosis, Ki-67 or polo-like kinase 1. Only nuclear cyclin B1 was significantly associated with adverse clinical outcome of the patients, and multivariate analyses of disease-free and overall survival demonstrated nuclear cyclin B1 as the independent marker. A similar tendency was detected in the patients receiving adjuvant therapy after surgery. These results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo-like kinase 1 and 14-3-3sigma. Nuclear cyclin B1-positive breast carcinoma is resistant to adjuvant therapy, and nuclear cyclin B1 immunoreactivity is a potent prognostic factor in breast carcinoma patients.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, 980-8575, Japan. suzuki@patholo2.med.tohoku.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Urano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis; D019926:Cyclin B / Q000032:analysis*; D056744:Cyclin B1; D005092:Exonucleases / Q000032:analysis; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D000097869:Polo-Like Kinase 1
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D005092:Exonucleases; D005095:Exoribonucleases; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D000097869:Polo-Like Kinase 1; C534699:CCNB1 protein, human; C489427:MYC protein, human; C413442:SFN protein, human