Microsatellite instability in medullary breast carcinomas

Microsatellite instability (MSI) has been reported to occur in a wide varie ty of sporadic tumours, such as colorectal and gastric cancers. MSI positiv ity has been associated with a particular clinico-pathologic profile, inclu ding the presence of abundant lymphoid infiltration, poor differentiation a nd a relatively good outcome for the patients. Since medullary breast carci nomas (MBCs) share these clinico-pathologic features with the MSI-positive tumours described above, we evaluated MSI in this particular histologic typ e of breast cancer. DNA of 24 MBC cases was extracted from formalin-fixed, paraffin-embedded tissue. The presence of MSI was analysed using BAT-26. We also searched mutations in 2 target genes: TGF-beta RII and BAX. Five case s of the series were also analysed for I (CA) dinucleotide tandem repeat se quence (D1S158), 8 tetranucleotide repeat sequences (D3S1358, D5S818, D7S82 0, D8S1179, D13S317, D21S11, FGA and VWA) and I pentanucleotide repeat (dAA AAT), localized in intron I of p53 gene. We found 2 carcinomas (8.3%) with BAT-26 instability. None of the cases had mutations in the "target genes", TGF-beta RII and BAX, including the 2 cases with BAT-26 instability. No MSI was observed using the panel of tetra- and pentanucleotide markers. Loss o f heterozygosity was found in some loci. No significant difference in mean MIB-I index according to RER status was observed. The low frequency of MSI in MBC is similar to that of other histologic types of breast cancer, Altho ugh MBCs share some clinico-pathologic features with colorectal and gastric carcinomas, which exhibit a high frequency of MSI, the underlying genetic events leading to this breast tumour are different from those leading to tu mours of the digestive tract. int, J. Cancer 82:644-647, 1999. (C) 1999 Wil ey-Liss, Inc.