Elsevier

The Breast

Volume 13, Issue 5, October 2004, Pages 383-388
The Breast

Original Article
Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer

https://doi.org/10.1016/j.breast.2004.02.010Get rights and content

Abstract

The modulation of Bmi-1 is observed in several tumor tissues, and its heightened protein level is suspected to be involved in tumorigenesis by acting as a transcriptional repressor in the INK4a/ARF locus. To elucidate the modulation of Bmi-1 in invasive ductal breast cancers, we examined its transcript and protein levels. The bmi-1 mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) showed that it was significantly up-regulated in 28 specimens out of 33 breast carcinoma tissues compared with those of non-neoplastic tissues just adjusted to tested specimens. Immunohistochemical staining for Bmi-1 also showed that 44 specimens out of 71 breast carcinoma tissues (62%) had strong positive signals with a more intense staining pattern in the invading fronts than in the central portions of 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 positive estrogen receptor status. These findings suggested that Bmi-1 might be involved in the tumor progression and metastasis of invasive ductal breast cancer.

Introduction

Breast carcinoma is one of the most common malignancies affecting women worldwide. The pathogenic mechanism underlying development and progression of breast carcinoma is still largely unknown. The bmi-1 putative oncogene belonging to the mammalian polycomb group family forms multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, cell cycle regulation, and senescence.1., 2., 3. It was first identified as an oncogene that cooperates with c-myc in the generation of mouse pre B-cell lymphomas.4., 5. It has been reported that Bmi-1 contributes to cell cycle regulation by acting as a stable transcriptional repressor of the INK4a/ARF (=human p19ARF) locus.6., 7. Inactivation of the p16INK4a-pRb pathway and p14ARF-MDM2-p53 pathway by bmi-1 deregulation has been clearly implicated in the lymphomagenesis8., 9., 10. and oncogenesis in non-small-cell lung cancer of humans.11 Recently, it has been shown that bmi-1 overexpression leads to activation of human telomerase reverse transcriptase transcription and induction of telomerase activity in immortalized mammary epithelial cells.12 However, there is little information available about the expression of Bmi-1 in a series of human breast carcinoma.

In this study, we tried to reveal the correlations between the expression of Bmi-1 and the various clinicopathologic factors, such as age, lymph node metastases, estrogen receptor (ER), and progesterone receptor (PR), in invasive ductal carcinoma of the breast.

Section snippets

Patients and specimens

The 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. Patients included in the study had an axillary dissection that sampled at least five lymph nodes. The cancerous breast and paired normal breast tissues taken from a site distant from the tumorous lesion were snap-frozen and stored in liquid nitrogen until further use. For the immunohistochemical study, some of

Bmi-1 expression in invasive ductal breast cancer

The relative levels of expression of the bmi-1 in 33 breast carcinoma tissues were compared with those of non-tumorous tissues by RT-PCR. The expression levels were determined as a ratio between the bmi-1 and the reference gene (GAPDH) to correct for the variation in the amounts of mRNA. The bmi-1 mRNA level was significantly increased (P<0.0001) in 28 specimens out of the examined 33 human breast carcinomas compared with that in their corresponding specimens of normal breast tissue (Fig. 1A

Discussion

Breast cancer has been increasing steadily in frequency, and many patients have suffered this malignancy have during the last few decades. The available clinicopathologic prognostic indicators are not accurate; despite axillary nodal status being the most important factor that determines the overall survival in patients with breast cancer, approximately 25–30% of node-negative cases eventually relapse.15 Thus, it is important to identify a biological genetic molecular marker that is associated

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