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Open Access Highly Accessed Research article

Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

Margit LH Riis12, Torben Lüders2, Anne-Jorunn Nesbakken3, Hilde S Vollan2, Vessela Kristensen2* and Ida RK Bukholm14

Author Affiliations

1 Department of Surgery, Akershus University Hospital, Lørenskog, Norway

2 Department of Clinical Molecular Biology (EpiGen), Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway

3 Department of Pathology, Akershus University Hospital, Lørenskog, Norway

4 Institute of Clinical Medicine, University of Oslo, Lørenskog, Norway

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BMC Cancer 2010, 10:686  doi:10.1186/1471-2407-10-686

Published: 16 December 2010

Abstract

Background

Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women.

Methods

A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry.

Results

Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer.

Conclusion

Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.