title: Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.
abstract: Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the molecular level to pure mucinous cancers, suggesting that mixed mucinous carcinomas may be best classified as variants of mucinous cancers rather than of IDC-NSTs.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Paula H
authors.initials: PH
authors.lastname: Suarez
authors.forename: Alan
authors.initials: A
authors.lastname: MacKay
authors.forename: Maryou B
authors.initials: MB
authors.lastname: Lambros
authors.forename: Rachael
authors.initials: R
authors.lastname: Natrajan
authors.forename: Kay
authors.initials: K
authors.lastname: Savage
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009857:Oncogenes
chemical_list: D009363:Neoplasm Proteins