title: Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis.
abstract: OBJECTIVE
  Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas.
  
  
  RESULTS
  Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development.
  
  
  CONCLUSIONS
  Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.
authors.affiliation: Molecular Pathology Team, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
authors.forename: Felipe C
authors.initials: FC
authors.lastname: Geyer
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Colombo
authors.forename: Neill
authors.initials: N
authors.lastname: Patani
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gauthier
authors.forename: Rachael
authors.initials: R
authors.lastname: Natrajan
authors.forename: Maryou B K
authors.initials: MB
authors.lastname: Lambros
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khalifeh
authors.forename: Constance
authors.initials: C
authors.lastname: Albarracin
authors.forename: Sandra
authors.initials: S
authors.lastname: Orru
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchiò
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D005348:Fibrocystic Breast Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor