Open Access Research article

Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes

Silvia Darb-Esfahani1*, Gunter von Minckwitz23, Carsten Denkert1, Beyhan Ataseven4, Bernhard Högel5, Keyur Mehta2, Gabriele Kaltenecker6, Thomas Rüdiger7, Berit Pfitzner1, Kornelia Kittel8, Bettina Fiedler9, Klaus Baumann10, Roland Moll11, Manfred Dietel1, Holger Eidtmann12, Christoph Thomssen13 and Sibylle Loibl4

Author Affiliations

1 Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

2 German Breast Group (GBG Forschungs GmbH), Neu-Isenburg, Germany

3 University Women’s Hospital, Frankfurt am Main, Germany

4 Department of Gynecology and Obstetrics Rotkreuzklinikum München, Munich, Germany

5 Instititue of Pathology Rotkreuzklinikum München, Munich, Germany

6 Department of Gynecology and Obstetrics, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

7 Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

8 Praxisklinik Berlin, Berlin, Germany

9 Institute of Pathology, Sana Klinikum Lichtenberg, Berlin, Germany

10 Department of Gynecology and Obstetrics, University Hospital Giessen/Marburg, Marburg, Germany

11 Insitute of Pathology, University Hospital Giessen/Marburg, Marburg, Germany

12 Department of Gynecology and Obstetrics, Universitätsklinikum Schleswig-Holstein, Kiel, Germany

13 Department of Gynecology, Universitätsklinikum Halle (Saale), Halle (Saale), Germany

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BMC Cancer 2014, 14:546  doi:10.1186/1471-2407-14-546

Published: 28 July 2014

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.

Keywords:
GCDFP-15; Breast cancer; Neoadjuvant chemotherapy; Apocrine; CUP