title: Absence of microsatellite instability in mucinous carcinomas of the breast.
abstract: Microsatellite instability (MSI) is a form of genetic instability that results from defects in DNA mismatch repair. MSI is reported to be rare in unselected breast cancers, however it is a common feature in subsets of colorectal, ovarian and endometrial cancers. In these anatomical sites, MSI-high carcinomas often display a mucinous histology. The aim of this study was to determine whether mucinous carcinomas of the breast would more frequently display MSI-high than invasive ductal carcinomas of no special type (IDC-NSTs). The expression of four MSI markers (i.e. MSH2, MSH6, MLH1 and PMS2) was immunohistochemically assessed in 35 mucinous breast carcinomas and 35 histological grade- and oestrogen receptor (ER) status-matched IDC-NSTs, and in a series of 245 invasive breast cancers. Cases were considered as potentially MSI-high if tumour cells lacked expression of at least two MSI markers and internal controls displayed nuclear staining. Nine mucinous carcinomas were microdissected and subjected to MSI analysis by PCR using the MSI markers BAT26 and BAT40. No immunohistochemical evidence of MSI-high was found in the 35 mucinous carcinomas and 35 grade- and ER-matched IDC-NSTs, and in the cohort of 245 invasive breast cancers. In addition, no evidence of MSI-high was observed by PCR analysis using the BAT26 and BAT40 markers in the nine mucinous carcinomas tested. Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous carcinomas of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.
authors.affiliation: Molecular Pathology Team, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, SW3 6JB, UK.
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Maryou B
authors.initials: MB
authors.lastname: Lambros
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.forename: Paula H
authors.initials: PH
authors.lastname: Suarez
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D045643:DNA Repair Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042282:Microdissection; D053842:Microsatellite Instability; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes