MICROSATELLITE INSTABILITY IN DUCTAL CARCINOMA IN-SITU OF THE BREAST

Microsatellite instability (MI+) is associated with defects in mismatc h repair, resulting in a 'mutator' phenotype and the development and p rogression of cancer. MI+ has been documented in invasive breast carci nomas. This study was undertaken to determine whether MI+ is found in the early non-invasive form of breast cancer, ductal carcinoma in situ (DCIS). We examined microdissected ducts from 23 cases of DCIS with 1 1 markers comprising mono-, di-, and trinucleotide repeats from six ch romosomal regions. Five tumours (22 per cent) displayed MI+ at two or more loci, in all ducts examined. A further seven (30 per cent) tumour s showed alterations at a single locus (the DM-1 trinucleotide), and f or two of these, heterogeneity between ducts was observed. Alterations at microsatellite repeat motifs in the coding regions of four cancer- associated genes (TGF beta RII, IGFIIR, BAX, and E2F-4) were not obser ved. Immunohistochemistry revealed that there was no loss of reactivit y: for the mismatch repair proteins, MLH1, MSH2, and PMS2, in the DCIS cases. In general, MI+ tumours and those with alterations at the DM-1 microsatellite were predominantly of higher nuclear grade and express ing c-erbB-2, suggesting that aberrations in DNA repair functions may lead to the acquisition of a more aggressive phenotype in breast cance r. (C) 1998 John Wiley & Sons, Ltd.