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 14-3-3σ σ σ σ, 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 14-3-3σ σ σ σ. 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. (Cancer Sci 2007; 98: 644-651)

High cyclin B1 expression is associated with poor survival in breast cancer

“…A further study with 56 invasive stage I -II cancers did not show any association between cyclin B1 expression and prognosis (Peters et al, 2004). A recent study with 109 breast cancers suggested that nuclear cyclin B1 expression was an independent prognostic factor (Suzuki et al, 2007).…”

Patterns of cyclin A and B1 immunostaining in papillary thyroid carcinoma

“…Numerous studies have also demonstrated the usefulness of the evaluation of cyclin B1 expression as a prognostic factor for breast cancer. The expression level correlated with tumour size, presence of distant metastases and disease free survival [17].…”

FoxM1 mediated resistance to gefitinib in non-smallcell lung cancer cells

“…These findings suggest that an increase of survivin in cancer cells would decrease chemotherapy sensitivity. Cyclin B1, a G 2 /mitotic-specific cyclin, is essential for the transition from G 2 to mitosis, and it has been implicated in the drug-resistance of several cancers [33,34] . For example, targeting cyclin B1 inhibits proliferation in several breast and cervical cancer cell lines, and sensitized breast cancer cells to paclitaxel [29] .…”

“…For example, targeting cyclin B1 inhibits proliferation in several breast and cervical cancer cell lines, and sensitized breast cancer cells to paclitaxel [29] . In addition, in head and neck squamous cell carcinomas, the overexpression of cyclin B1 correlates with radiotherapy resistance [34] , and nuclear cyclin B1-positive breast carcinomas are resistant to hormonal, radioand chemotherapy adjuvant treatment [33] .…”