Microsatellite instability in ductal carcinoma in situ of the breast.
Microsatellite instability (MI+) is associated with defects in mismatch repair, resulting in a 'mutator' phenotype and the development and progression of cancer. MI+ has been documented in invasive breast carcinomas. 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 11 markers comprising mono-, di-, and trinucleotide repeats from six chromosomal regions. Five tumours (22 per cent) displayed MI+ at two or more loci, in all ducts examined. A further seven (30 per cent) tumours showed alterations at a single locus (the DM-1 trinucleotide), and for 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 observed. Immunohistochemistry revealed that there was no loss of reactivity 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 expressing c-erbB-2, suggesting that aberrations in DNA repair functions may lead to the acquisition of a more aggressive phenotype in breast cancer.
Department of Pathology, University of Leicester, Glenfield Hospital, U.K.
T
T
Walsh
S A
SA
Chappell
J A
JA
Shaw
R A
RA
Walker
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53