title: Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes.
abstract: BACKGROUND
  Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated by the androgen receptor (AR), is a diagnostic marker for mammary differentiation in histopathology. We determined the expression of GCDFP-15 in breast cancer subtypes, its potential prognostic and predictive value, as well as its relationship to AR expression.
  
  
  METHODS
  602 pre-therapeutic breast cancer core biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765) were investigated for GCDFP-15 expression by immunohistochemistry. Expression data were correlated with disease-free (DFS) and overall survival (OS) time as well as pathological complete response (pCR) to neoadjuvant chemotherapy.
  
  
  RESULTS
  239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was positively linked to hormone receptor (HR) and HER2 positive tumor type, while most triple negative carcinomas were negative (p < 0.0001). GCDFP-15 was also strongly correlated to AR expression (p 0.001), and to the so-called molecular apocrine subtype (HR-/AR+, p < 0.0001). Higher rates of GCDFP-15 positivity were seen in tumors of lower grade (<0.0001) and negative nodal status (p = 0.008). GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15 negative tumors (DFS (p = 0.052) and OS (p = 0.044)), which was not independent from other factors in multivariate analysis. GCDFP-15 expression was not linked to pCR. Histological apocrine differentiation was frequent in molecular apocrine carcinomas (60.7%), and was associated with GCDFP-15 within this group (p = 0.039).
  
  
  CONCLUSIONS
  GCDFP-15 expression is higher in tumors with favorable prognostic features. GCDFP-15 expression is further a frequent feature of AR positive tumors and the molecular apocrine subtype. It might have reduced sensitivity as a diagnostic marker for mammary differentiation in triple negative tumors as compared to HR or HER2 positive tumor types.
authors: Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. silvia.darb-esfahani@charite.de.
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Gunter
authors: G
authors: von Minckwitz
authors: Carsten
authors: C
authors: Denkert
authors: Beyhan
authors: B
authors: Ataseven
authors: Bernhard
authors: B
authors: Högel
authors: Keyur
authors: K
authors: Mehta
authors: Gabriele
authors: G
authors: Kaltenecker
authors: Thomas
authors: T
authors: Rüdiger
authors: Berit
authors: B
authors: Pfitzner
authors: Kornelia
authors: K
authors: Kittel
authors: Bettina
authors: B
authors: Fiedler
authors: Klaus
authors: K
authors: Baumann
authors: Roland
authors: R
authors: Moll
authors: Manfred
authors: M
authors: Dietel
authors: Holger
authors: H
authors: Eidtmann
authors: Christoph
authors: C
authors: Thomssen
authors: Sibylle
authors: S
authors: Loibl
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D043823:Taxoids; C410798:AR protein, human; C488892:PIP protein, human; C080625:taxane; C508053:ERBB2 protein, human