Microsatellite instability in medullary breast carcinomas.
Microsatellite instability (MSI) has been reported to occur in a wide variety of sporadic tumours, such as colorectal and gastric cancers. MSI positivity has been associated with a particular clinico-pathologic profile, including the presence of abundant lymphoid infiltration, poor differentiation and a relatively good outcome for the patients. Since medullary breast carcinomas (MBCs) share these clinico-pathologic features with the MSI-positive tumours described above, we evaluated MSI in this particular histologic type 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 cases of the series were also analysed for 1 (CA) dinucleotide tandem repeat sequence (D1S158), 8 tetranucleotide repeat sequences (D3S1358, D5S818, D7S820, D8S1179, D13S317, D21S11, FGA and VWA) and 1 pentanucleotide repeat (dAAAAT), localized in intron 1 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 of heterozygosity was found in some loci. No significant difference in mean MIB-1 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. Although 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 tumours of the digestive tract.
Schmitt
F C
FC
Institute of Molecular Pathology and Immunology of the University of Porto, IPATIMUP, Porto, Portugal. fernando.schmitt@ipatimup.pt
Soares
R
R
Gobbi
H
H
Milanezzi
F
F
Santos-Silva
F
F
Cirnes
L
L
Costa
C
C
Seruca
R
R
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II