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Clinical Trial
. 2014 Jul 28:14:546.
doi: 10.1186/1471-2407-14-546.

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

Silvia Darb-Esfahani  1 , Gunter von Minckwitz, Carsten Denkert, Beyhan Ataseven, Bernhard Högel, Keyur Mehta, Gabriele Kaltenecker, Thomas Rüdiger, Berit Pfitzner, Kornelia Kittel, Bettina Fiedler, Klaus Baumann, Roland Moll, Manfred Dietel, Holger Eidtmann, Christoph Thomssen, Sibylle Loibl
Affiliations
Clinical Trial

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

Silvia Darb-Esfahani et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Immunohistochemical expression pattern of GCDFP-15 in breast cancer. A Tumor cells of an invasive lobular carcinoma, arranged in indian file pattern and exhibiting moderate cytoplasmic staining for GDCFP-15 B Solid carcinoma nests with patchy, mosaic-like pattern of GCDFP-15 expression C Diffuse GCDFP-15 expression in a poorly differentiated ductal carcinoma D Distribution of GCDFP-15 immunoreactivity scores (IRS) in the study group. The majority of cases did not display any staining (IRS = 0); in the remaining carcinomas, IRS values were equally distributed; the cut-off was set between IRS = 0 and IRS = 2.
Figure 3
Figure 3
Morphology of molecular apocrine carcinomas. A Apocrine carcinoma with abundant eosinophilic granular cytoplasm exhibiting diffuse GCDFP-15 expression (insert) B Pleomorphic lobular carcinoma with dyscohesive growth of large cells with highly atypical nuclei and eosinophilic granular cytoplasm, strong diffuse GCDFP-15 expression is seen by immunohistochemistry (insert).
Figure 4
Figure 4
Survival analysis A, B DFS and OS in dependence of GCDFP-15 expression in the study group.
See this image and copyright information in PMC

References

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Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/546/prepub

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