Association of Elevated Peripheral Blood Micronucleus Frequency and Bmi-1 mRNA Expression with Metastasis in Iranian Breast Cancer Patients

BACKGROUND: In order to find cytogenetic and molecular metastasis biomarkers detectable in peripheral blood the spontaneous genomic instability expressed as micronuclei and Bmi-1 expression in peripheral blood of breast cancer (BC) patients were studied in different stages of the disease compared with unaffected first-degree relatives (FDRs) and normal control. METHODS: The Cytokinesis Block Micronuclei Cytome (CBMN cyt) and nested real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays, were respectively used to measure genomic instability and Bmi-1 gene expression in 160 Iranian individuals comprised of BC patients in different stages of the disease, unaffected FDRs and normal control groups. RESULT: The frequency of micronuclei and Bmi-1 expression were dramatically higher in distant metastasis compared with non-metastatic BC. In spite of micronucleus frequency with no association with lymph node (LN) involvement and hormone receptor status, the Bmi-1 expression level was higher in LN positive and triple negative patients. CONCLUSION: Our results indicate that increased genomic instability expressed as micronuclei and higher Bmi-1 expression in peripheral blood are associated with metastasis in breast cancer. Therefore implementation of micronucleus assay and Bmi-1 expression analysis in blood as possible cytogenetic and molecular biomarkers in clinical level may potentially enhance the quality of management of patients with breast cancer.