Breast Cancer Research and Treatment 60: 135–142, 2000. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. Report Microsatellite instability markers in breast cancer: A review and study showing MSI was not detected at ‘BAT 25’ and ‘BAT 26’ microsatellite markers in early-onset breast cancer Shoo Peng Siah 1,2 , Diana M Quinn 1 , Graeme D Bennett 2 , Graeme Casey 2 , Robert LP Flower 1 , Graeme Suthers 3 , and Zbigniew Rudzki 2 1 School of Pharmacy and Medical Science, University of South Australia, City East Campus, Adelaide; 2 Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide; 3 South Australia Clinical Genetics Services, Women’s and Children’s Hospital, North Adelaide, Australia Key words: breast cancer, microsatellite instability, microsatellite markers, review, survey Summary Microsatellite markers may provide evidence of faulty DNA mismatch repair (MMR) via the detection of mi- crosatellite instability (MSI). The choice of microsatellite markers may impact on the MSI detection rate. In hereditary non-polyposis colon cancer (HNPCC), several informative microsatellite markers have been recom- mended. Two of these, BAT 25 and BAT 26, are quasi-homozygous, enabling analysis of tumour DNA in the absence of paired normal DNA. Sixty-six breast cancer patients under 45 years of age at diagnosis were examined for MSI at BAT 25 and BAT 26. Tumour DNA was extracted from paraffin-embedded tissue. No MSI was detected at the BAT 25 or BAT 26 loci. An additional five microsatellite markers, known to be informativefor HNPCC, were examined for MSI in these patients. Apparently-normal profiles were achieved. A tabulated survey of 306 microsatellite markers used to detect MSI in breast cancer revealed that only 35.5% of markers detected MSI at an average rate of 2.9%. The MSI detection rate at the specific HNPCC markers varied from 0% to 10% in breast cancer, with D175250 and TP53 being the HNPCC markers most suitable for analysis of breast cancer. The size of the microsatellite marker’s repeat unit did not impact on MSI detection rates. Compiled data from large studies (n> 100) revealed D115988 as the marker with the highest MSI detection rate. Genomic instability pathways of carcinogenesis, characterised by MMR defects and MSI, appear to play a role in the genesis of some breast cancer types. Introduction Microsatellites are repeat regions of one to six nucle- otide units that occur primarily in non-coding regions of DNA [1]. The number of microsatellite repeat units located at a given locus is genetically determined [2]. These highly repetitive regions of DNA are difficult for DNA polymerase to faithfully reproduce during DNA synthesis [1]. Slippage may occur with copies of the repeat unit being inserted or deleted, thereby alter- ing the size of the locus [1]. Normally, the integrity of the genome is monitored by a number of mechanisms, one of which is involved in the detection and correc- tion of DNA mismatches – the DNA mismatch repair (MMR) mechanism. Defects in DNA MMR mechanisms have been shown to be a feature of the familial disorder hered- itary non-polyposis colorectal cancer (HNPCC) [1, 3]. A common characteristic of this defect is the observa- tion of instability at microsatellite markers in tumour DNA. Microsatellite instability (MSI) can be detected by demonstration of variability in the number of re- peat units in selected microsatellite markers following amplification using polymerase chain reaction (PCR)