Overexpression of the Bmi-1 Oncoprotein correlates with Axillary Lymph Node Metastases in Invasive Ductal Breast Cancer

摘要

Purpose The modulation of Bmi-1 is observed in several tumor tissues, with its heightened protein level suspected of being involved in tumorigenesis by acting as a transcriptional repressor in the INK4a/ ARF locus. To elucidate the role of Bmi-1 in invasive ductal breast cancers, the expression of Bmi-1 at the mRNA and protein levels were examined. Methods Breast carcinoma samples were obtained from patients who underwent routine surgery for breast cancer at the Department of Surgery, Chonbuk National University Hospital, in 2000-2002. Cancerous breast and paired normal breast tissues were taken from a site distant from the tumorous lesion, and analyzed with reverse transcription-polymerase chain reaction (RT-PCR) and and immunohistochemical assay. We analyzed the correlations between the expression of Bmi-1 and various clinicopathological factors, such as age, lymph node metastases, estrogen receptor (ER), and progesterone receptor (PR), in invasive ductal carcinomas of the breast. Results The Bmi-1 mRNA level by RT-PCR was shown to be significantly up-regulated in 19 of the 22 breast carcinoma tissues specimen compared with the non-neoplastic tissues adjusted to tested specimens. The immunohistochemical staining for Bmi-1 also showed high a level of expression in 44 of the 71 invasive ductal breast cancers (62%), and was more intense in the invading fronts than in the central portions of the primary invasive breast cancers. Univariate and multivariate analyses showed that a high level of Bmi-1 expression was significantly correlated with axillary lymph node metastases and a positive estrogen receptor status. Conclusion The Bmi-1 was differentially expressed in human breast carcinomas. These findings suggested that Bmi-1 might be involved in the progression of invasive ductal breast cancer, and it may be clinically useful in selecting patients who could benefit from adjuvant chemotherapy.