Abstract
BackgroundGross 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.Methods602 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.Results239 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).ConclusionsGCDFP-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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-546) contains supplementary material, which is available to authorized users.
Highlights
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 investigated the expression of GCDFP-15 in a large and well-characterized clinical trial cohort of breast carcinomas treated with neoadjuvant chemotherapy (NACT) with a special emphasis on its distribution in breast cancer subtypes and its prognostic impact
Our study thereby confirms previous findings of an association between GCDFP-15 expression and features of good-prognosis tumors [7,22,26], and it might be speculated that GCDFP-15 parallels the expression of its regulatory factor AR, which is linked to favorable prognostic clinico-pathological features, as we showed previously [20]
Summary
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. Prolactin-inducible protein, PIP) is a 15 kDa protein that was originally detected in the cystic fluid from cystic mastopathy [1] It is not expressed in normal ductal or lobular epithelium but in apocrine metaplasia of the breast [2]. Apart from breast cancer, only very few tumors, such as prostate cancer and carcinomas of the skin appendages express GCDFP-15 [3]. It is carcinoma, which is primarily defined by morphological features such as abundant eosinophilic and granular cytoplasm, and shows frequent expression of the androgen receptor (AR) [10].
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