Absence of Microsatellite Instability in Mucinous Carcinomas of the Breast.
Magali Lacroix-Triki, Maryou B Lambros, Felipe C Geyer, Paula H Suarez, Jorge S Reis-Filho, Britta Weigelt. Institute of Cancer Research, London, United Kingdom; Institut Claudius Regaud, Toulouse, France; Cancer Research UK, London Research Institute, United Kingdom
Background: Mucinous carcinomas of the breast have been shown to be distinct from invasive ductal carcinomas of no special type (IDC-NSTs) at the genomic and transcriptomic levels. Previous studies have demonstrated a relative paucity of chromosomal copy number aberrations in mucinous carcinomas. Microsatellite instability (MSI) is a form of genetic instability that often results from defects in mismatch repair. Whilst reported as uncommon in breast cancer, it is a prominent feature of subsets of colorectal, ovarian and endometrial tumours, particularly in the context of Lynch syndrome, where it has been associated in particular with tumours of mucinous histology. In addition, MSI-high tumours have been shown to have few chromosomal copy number aberrations. The aims of this study were to determine whether a subset of mucinous carcinomas of the breast would display MSI, and whether mucinous carcinomas would more frequently display an MSI-high phenotype than IDC-NSTs.
Design: Thirty-five mucinous breast carcinomas and a cohort of 245 invasive breast cancers, of which 180 IDC-NSTs, were assessed by immunohistochemistry on tissue microarray using the MSI markers MSH2, MSH6, MLH1 and PMS2. In addition, nine cases of mucinous carcinomas were microdissected and subjected to MSI analysis by PCR for the MSI-high markers BAT26 and BAT40.
Results: None of the mucinous carcinomas studied here showed any MSI-high phenotype by immunohistochemistry, as defined by complete absence of expression of at least two markers. Among the mucinous carcinomas, 100%, 94.3%, 100% and 94.1% were positive for MLH1, MSH2, MSH6 and PMS2 respectively. Consistent with these results, none of the mucinous cancers displayed MSI using two validated markers of MSI-high (i.e. BAT26 and BAT40). Out of the 245 invasive breast cancers analysed, four cases (1.6%) were negative for two markers, two of which were successfully retested on full sections and were finally recorded as microsatellite stable. Subgroup analysis of the 180 IDC-NSTs revealed that three cases (1.7%) were negative for two markers, one of which was shown to be microsatellite stable. The remaining two cases were recorded as inconclusive as full sections were not available for retesting.
Conclusions: Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous cancers of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 17, Tuesday Afternoon