title: Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer.
abstract: BACKGROUND
  The BRCA1 protein makes mammary stem cells differentiate into mature luminal and myoepithelial cells. If a BRCA1 mutation results in a differentiation block, an enlarged stem cell component might be present in the benign tissue of BRCA1 mutation carriers, and these mammary stem cells could be the origin of BRCA1 related breast cancer. Since ALDH1 is a marker of both mammary stem cells and breast cancer stem cells, we compared ALDH1 expression in malignant tissue of BRCA1 mutation carriers to non-carriers.
  
  
  METHODS
  Forty-one BRCA1 related breast cancers and 41 age-matched sporadic breast cancers were immunohistochemically stained for ALDH1. Expression in epithelium and stroma was scored and compared.
  
  
  RESULTS
  Epithelial (P = 0.001) and peritumoral (P = 0.001) ALDH1 expression was significantly higher in invasive BRCA1 related carcinomas compared to sporadic carcinomas. Intratumoral stromal ALDH1 expression was similarly high in both groups. ALDH1 tumor cell expression was an independent predictor of BRCA1 mutation status.
  
  
  CONCLUSIONS
  BRCA1 related breast cancers showed significantly more frequent epithelial ALDH1 expression, indicating that these hereditary tumors have an enlarged cancer stem cell component. Besides, (peritumoral) stromal ALDH1 expression was also more frequent in BRCA1 mutation carriers. ALDH1 may therefore be a diagnostic marker and a therapeutic target of BRCA1 related breast cancer.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Marise R
authors.initials: MR
authors.lastname: Heerma van Voss
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
authors.forename: Joost
authors.initials: J
authors.lastname: Bart
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D019313:BRCA1 Protein / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D015415:Biomarkers; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase