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

Youn, Hyun Jo; Jung, Sung Hoo

Abstract

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.