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Microsatellite instability in ductal carcinoma in situ of the breast
Author(s) -
Walsh Tom,
Chappell Stephen A.,
Shaw Jacqui A.,
Walker Rosemary A.
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199805)185:1<18::aid-path41>3.0.co;2-g
Subject(s) - microsatellite instability , ductal carcinoma , msh2 , biology , mlh1 , breast cancer , pms2 , locus (genetics) , pathology , microsatellite , loss of heterozygosity , cancer research , immunohistochemistry , phenotype , cancer , dna mismatch repair , genetics , colorectal cancer , medicine , gene , allele , immunology
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 β 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‐ erb B‐2, suggesting that aberrations in DNA repair functions may lead to the acquisition of a more aggressive phenotype in breast cancer. © 1998 John Wiley & Sons, Ltd.