title: Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15.
abstract: BACKGROUND
  Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors.
  
  
  METHODS
  We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features.
  
  
  RESULTS
  MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors.
  
  
  CONCLUSIONS
  MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hamy
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
authors.forename: Marc
authors.initials: M
authors.lastname: Barritault
authors.forename: Fatiha
authors.initials: F
authors.lastname: Bouhidel
authors.forename: Hanadi
authors.initials: H
authors.lastname: Habuellelah
authors.forename: Solenne
authors.initials: S
authors.lastname: Leman-Detours
authors.forename: Anne
authors.initials: A
authors.lastname: de Roquancourt
authors.forename: Laurence
authors.initials: L
authors.lastname: Cahen-Doidy
authors.forename: Edwige
authors.initials: E
authors.lastname: Bourstyn
authors.forename: Patricia
authors.initials: P
authors.lastname: de Cremoux
authors.forename: Cedric
authors.initials: C
authors.lastname: de Bazelaire
authors.forename: Marcela
authors.initials: M
authors.lastname: Albiter
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giacchetti
authors.forename: Caroline
authors.initials: C
authors.lastname: Cuvier
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Marc
authors.initials: M
authors.lastname: Espié
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertheau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001050:Apocrine Glands / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C488892:PIP protein, human; C508053:ERBB2 protein, human