Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Silvia Darb-Esfahani, 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

Published in: BMC Cancer | Issue 1/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Haagensen DE, Mazoujian G, Holder WD, Kister SJ, Wells SA: Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients. Ann Surg. 1977, 185: 279-285.CrossRefPubMedPubMedCentral Haagensen DE, Mazoujian G, Holder WD, Kister SJ, Wells SA: Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients. Ann Surg. 1977, 185: 279-285.CrossRefPubMedPubMedCentral
2.
go back to reference Mazoujian G, Pinkus GS, Davis S, Haagensen DE: Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features. Am J Pathol. 1983, 110: 105-112.PubMedPubMedCentral Mazoujian G, Pinkus GS, Davis S, Haagensen DE: Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features. Am J Pathol. 1983, 110: 105-112.PubMedPubMedCentral
3.
go back to reference Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT: Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989, 20: 281-287.CrossRefPubMed Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT: Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989, 20: 281-287.CrossRefPubMed
4.
go back to reference Loos S, Schulz KD, Hackenberg R: Regulation of GCDFP-15 expression in human mammary cancer cells. Int J Mol Med. 1999, 4: 135-140.PubMed Loos S, Schulz KD, Hackenberg R: Regulation of GCDFP-15 expression in human mammary cancer cells. Int J Mol Med. 1999, 4: 135-140.PubMed
5.
go back to reference Debily MA, Marhomy SE, Boulanger V, Eveno E, Mariage-Samson R, Camarca A, Auffray C, Piatier-Tonneau D, Imbeaud S: A functional and regulatory network associated with PIP expression in human breast cancer. PLoS One. 2009, 4: e4696-CrossRefPubMedPubMedCentral Debily MA, Marhomy SE, Boulanger V, Eveno E, Mariage-Samson R, Camarca A, Auffray C, Piatier-Tonneau D, Imbeaud S: A functional and regulatory network associated with PIP expression in human breast cancer. PLoS One. 2009, 4: e4696-CrossRefPubMedPubMedCentral
6.
go back to reference Vranic S, Schmitt F, Sapino A, Costa JL, Reddy S, Castro M, Gatalica Z: Apocrine carcinoma of the breast: a comprehensive review. Histol Histopathol. 2013, 28: 1393-409.PubMed Vranic S, Schmitt F, Sapino A, Costa JL, Reddy S, Castro M, Gatalica Z: Apocrine carcinoma of the breast: a comprehensive review. Histol Histopathol. 2013, 28: 1393-409.PubMed
7.
go back to reference Honma N, Takubo K, Akiyama F, Sawabe M, Arai T, Younes M, Kasumi F, Sakamoto G: Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast. Histopathology. 2005, 47: 195-201.CrossRefPubMed Honma N, Takubo K, Akiyama F, Sawabe M, Arai T, Younes M, Kasumi F, Sakamoto G: Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast. Histopathology. 2005, 47: 195-201.CrossRefPubMed
8.
go back to reference Honma N, Takubo K, Arai T, Younes M, Kasumi F, Akiyama F, Sakamoto G: Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast. APMIS. 2006, 114: 712-719.CrossRefPubMed Honma N, Takubo K, Arai T, Younes M, Kasumi F, Akiyama F, Sakamoto G: Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast. APMIS. 2006, 114: 712-719.CrossRefPubMed
9.
go back to reference Eusebi V, Millis RR, Cattani MG, Bussolati G, Azzopardi JG: Apocrine carcinoma of the breast. A morphologic and immunocytochemical study. Am J Pathol. 1986, 123: 532-541.PubMedPubMedCentral Eusebi V, Millis RR, Cattani MG, Bussolati G, Azzopardi JG: Apocrine carcinoma of the breast. A morphologic and immunocytochemical study. Am J Pathol. 1986, 123: 532-541.PubMedPubMedCentral
10.
go back to reference Vranic S, Tawfik O, Palazzo J, Bilalovic N, Eyzaguirre E, Lee LM, Adegboyega P, Hagenkord J, Gatalica Z: EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast. Mod Pathol. 2010, 23: 644-653.CrossRefPubMed Vranic S, Tawfik O, Palazzo J, Bilalovic N, Eyzaguirre E, Lee LM, Adegboyega P, Hagenkord J, Gatalica Z: EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast. Mod Pathol. 2010, 23: 644-653.CrossRefPubMed
11.
go back to reference Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R: Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005, 24: 4660-4671.CrossRefPubMed Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R: Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005, 24: 4660-4671.CrossRefPubMed
12.
go back to reference Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL: An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene. 2006, 25: 3994-4008.CrossRefPubMed Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL: An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene. 2006, 25: 3994-4008.CrossRefPubMed
13.
go back to reference Sanga S, Broom BM, Cristini V, Edgerton ME: Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med Genomics. 2009, 11: 59-CrossRef Sanga S, Broom BM, Cristini V, Edgerton ME: Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med Genomics. 2009, 11: 59-CrossRef
14.
go back to reference von Minckwitz G, Blohmer JU, Raab G, Löhr A, Gerber B, Heinrich G, Eidtmann H, Kaufmann M, Hilfrich J, Jackisch C, Zuna I, Costa SD: In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol. 2005, 16: 56-63.CrossRefPubMed von Minckwitz G, Blohmer JU, Raab G, Löhr A, Gerber B, Heinrich G, Eidtmann H, Kaufmann M, Hilfrich J, Jackisch C, Zuna I, Costa SD: In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol. 2005, 16: 56-63.CrossRefPubMed
15.
go back to reference von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M: Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008, 100: 552-562.CrossRefPubMed von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M: Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008, 100: 552-562.CrossRefPubMed
16.
go back to reference von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M: Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008, 100: 542-551.CrossRefPubMed von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M: Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008, 100: 542-551.CrossRefPubMed
17.
go back to reference von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Kümmel S, Paepke S, Schneeweiss A, Untch M, Zahm DM, Mehta K, Loibl S: Response-Guided Neoadjuvant Chemotherapy for Breast Cancer. J Clin Oncol. 2013, 31: 3623-3630.CrossRefPubMed von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Kümmel S, Paepke S, Schneeweiss A, Untch M, Zahm DM, Mehta K, Loibl S: Response-Guided Neoadjuvant Chemotherapy for Breast Cancer. J Clin Oncol. 2013, 31: 3623-3630.CrossRefPubMed
18.
go back to reference Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF: American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007, 25: 118-145.CrossRefPubMed Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF: American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007, 25: 118-145.CrossRefPubMed
19.
go back to reference Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC: American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010, 28: 2784-2795.CrossRefPubMedPubMedCentral Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC: American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010, 28: 2784-2795.CrossRefPubMedPubMedCentral
20.
go back to reference Loibl S, Müller BM, von Minckwitz G, Schwabe M, Roller M, Darb-Esfahani S, Ataseven B, du Bois A, Fissler-Eckhoff A, Gerber B, Kulmer U, Alles JU, Mehta K, Denkert C: Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2011, 130: 477-487.CrossRefPubMed Loibl S, Müller BM, von Minckwitz G, Schwabe M, Roller M, Darb-Esfahani S, Ataseven B, du Bois A, Fissler-Eckhoff A, Gerber B, Kulmer U, Alles JU, Mehta K, Denkert C: Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2011, 130: 477-487.CrossRefPubMed
21.
go back to reference Huo L, Zhang J, Gilcrease MZ, Gong Y, Wu Y, Zhang H, Resetkova E, Hunt KK, Deavers MT: Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer. Histopathology. 2013, 62: 267-274.CrossRefPubMed Huo L, Zhang J, Gilcrease MZ, Gong Y, Wu Y, Zhang H, Resetkova E, Hunt KK, Deavers MT: Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer. Histopathology. 2013, 62: 267-274.CrossRefPubMed
22.
go back to reference Lewis GH, Subhawong AP, Nassar H, Vang R, Illei PB, Park BH, Argani P: Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin. Am J Clin Pathol. 2011, 135: 587-591.CrossRefPubMedPubMedCentral Lewis GH, Subhawong AP, Nassar H, Vang R, Illei PB, Park BH, Argani P: Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin. Am J Clin Pathol. 2011, 135: 587-591.CrossRefPubMedPubMedCentral
23.
go back to reference Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF, de Jong D, Van de Vijver MJ, Van't Veer LJ, Peterse JL: Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008, 216: 141-150.CrossRefPubMed Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF, de Jong D, Van de Vijver MJ, Van't Veer LJ, Peterse JL: Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008, 216: 141-150.CrossRefPubMed
24.
go back to reference Pagani A, Sapino A, Eusebi V, Bergnolo P, Bussolati G: PIP/GCDFP-15 gene expression and apocrine differentiation in carcinomas of the breast. Virchows Arch. 1994, 425: 459-465.CrossRefPubMed Pagani A, Sapino A, Eusebi V, Bergnolo P, Bussolati G: PIP/GCDFP-15 gene expression and apocrine differentiation in carcinomas of the breast. Virchows Arch. 1994, 425: 459-465.CrossRefPubMed
25.
go back to reference Fritzsche FR, Thomas A, Winzer KJ, Beyer B, Dankof A, Bellach J, Dahl E, Dietel M, Kristiansen G: Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer. Histol Histopathol. 2007, 22: 1221-1230.PubMed Fritzsche FR, Thomas A, Winzer KJ, Beyer B, Dankof A, Bellach J, Dahl E, Dietel M, Kristiansen G: Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer. Histol Histopathol. 2007, 22: 1221-1230.PubMed
26.
go back to reference Luo MH, Huang YH, Ni YB, Tsang JY, Chan SK, Shao MM, Tse GM: Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas. Hum Pathol. 2013, 44: 1241-1250.CrossRefPubMed Luo MH, Huang YH, Ni YB, Tsang JY, Chan SK, Shao MM, Tse GM: Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas. Hum Pathol. 2013, 44: 1241-1250.CrossRefPubMed
27.
go back to reference Hall RE, Clements JA, Birrell SN, Tilley WD: Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours. Br J Cancer. 1998, 78: 360-365.CrossRefPubMedPubMedCentral Hall RE, Clements JA, Birrell SN, Tilley WD: Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours. Br J Cancer. 1998, 78: 360-365.CrossRefPubMedPubMedCentral
28.
go back to reference Lakhani S, Ellis IO, Tan PH, van de Vijver MJ: WHO Classification of Tumors of the Breast. 2012, Lyon: IARC Press Lakhani S, Ellis IO, Tan PH, van de Vijver MJ: WHO Classification of Tumors of the Breast. 2012, Lyon: IARC Press
Metadata
Title
Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes
Authors
Silvia Darb-Esfahani
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
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-546

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine