Gross cystic disease fluid protein 15 (GCDFP-15)

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Stains & CD markers
Gross cystic disease fluid protein 15 (GCDFP-15)

Authors: Joshua J.X. Li, M.B.Ch.B., Gary M. Tse, M.B.B.S.

Editorial Board Member: Julie M. Jorns, M.D.

Deputy Editor-in-Chief: Gary Tozbikian, M.D.

Last author update: 17 April 2024

Last staff update: 17 April 2024

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: GCDFP-15

Table of Contents

Cite this page: Li JJX, Tse GM. Gross cystic disease fluid protein 15 (GCDFP-15). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsgcdfp15.html. Accessed December 21st, 2024.

Definition / general

A marker of apocrine differentiation
Present in breast, salivary and seminal secretions with possible functions in breast carcinogenesis (Adv Exp Med Biol 2015;846:189, PLoS One 2009;4:e4696)

Essential features

A marker of apocrine differentiation
Positive mainly in breast and salivary gland lesions
Useful in confirming breast primary in metastatic carcinomas but sensitivity is lower than GATA3

Terminology

BRST2
Prolactin inducible protein (PIP)

Pathophysiology

Expression of GCDFP-15 is regulated by androgen receptor (Int J Mol Med 1999;4:135)
Gene expression profiling revealed associations between PIP gene and cell adhesion, apoptosis and proliferation in breast cancer cells (PLoS One 2009;4:e4696)

Clinical features

Blood levels of GCDFP-15 were elevated in a small subgroup of patients with benign (cyst) and malignant (preinvasive and invasive carcinoma) breast diseases (The Breast 1997;6:113, Int J Cancer 1999;84:568)

Interpretation

Cytoplasmic staining

Uses by pathologists

Confirming apocrine differentiation in breast and salivary gland lesions (Virchows Arch 2022;480:177)
Confirming breast or salivary gland primary in metastatic carcinomas (J Mol Pathol 2022;3:219, Semin Diagn Pathol 2022;39:313)
- Less sensitive than GATA3 and mammaglobin for hormone receptor positive breast cancers
- Less sensitive than SOX10 for hormone receptor negative breast cancers
- Less sensitive than TRPS1 for hormone receptor positive, nonapocrine HER2 positive and triple negative breast cancers
Diagnosis of salivary gland carcinomas including salivary duct carcinoma and acinic cell carcinoma
Differentiating primary extramammary Paget disease (positive) from secondary extramammary Paget disease (negative) (Arch Pathol Lab Med 1998;122:1077)

Prognostic factors

GCDFP-15 stain expression in breast cancer offers no independent prognostic value over hormone markers (BMC Cancer 2014;14:546)

Microscopic (histologic) images

Contributed by Joshua J.X. Li, M.B.Ch.B. and Gary M. Tse, M.B.B.S.

Breast apocrine glands

Apocrine ductal carcinoma in situ

Metastatic breast cancer

Salivary gland

Salivary duct carcinoma

Virtual slides

Images hosted on other servers:

Hidradenoma papilliferum

Extramammary Paget disease

Apocrine ductal carcinoma in situ

Positive staining - normal

Apocrine glands, including Moll glands (breast, ear canal, eyelid, skin) (Am J Pathol 1983;110:105)
Serous glands (bronchus, nasal cavity, lacrimal gland, salivary gland) (Am J Pathol 1983;110:105)
Ceruminous glands (Virchows Arch 1998;432:255)
Eccrine glands (Virchows Arch 1998;432:255)

Positive staining - disease

Breast (BMC Cancer 2014;14:546, Mod Pathol 2001;14:768)
- Androgen receptor positive (apocrine differentiation) (52%)
- Invasive lobular carcinoma (52%)
- Mucinous carcinoma (54%)
- Solid papillary carcinoma (66%)
- Other factors favoring GCDFP-15 expression are HER2 positivity, old age and low histological grade
Salivary gland neoplasms
- Pleomorphic adenoma (luminal cells) (81%) (Arch Pathol Lab Med 1991;115:158)
- Salivary duct carcinoma (100%) (Mod Pathol 1998;11:1033)
- Secretory carcinoma (75%) (J Oral Pathol Med 2015;44:244)
Cutaneous neoplasms
- Primary extramammary Paget disease (Arch Pathol Lab Med 1998;122:1077)
- Papillary hidradenoma (Arch Pathol Lab Med 1991;115:1249)

Negative staining

Secondary extramammary Paget disease (Hum Pathol 2002;33:545)
Adenoid cystic carcinoma (Arch Pathol Lab Med 1991;115:158)
Mucoepidermoid carcinoma (17%) (Hum Pathol 1989;20:281)
Polymorphous low grade adenocarcinoma (Arch Pathol Lab Med 1991;115:158)
Secretory carcinoma of the breast (Mod Pathol 2012;25:567)
Prostate adenocarcinoma (10%) (Hum Pathol 1989;20:281)

Sample pathology report

Lung nodule, core needle biopsy:
- Metastatic carcinoma, consistent with breast primary (see comment)
- Comment: Sections show clusters and nests of tumor cells with a moderate amount of cytoplasm, hyperchromatic irregular nuclei and occasional distinct nucleoli. The tumor cells show immunoreactivity to GATA3, GCDFP-15 and estrogen receptor, supporting a breast primary.

Board review style question #1

Which of the following is true about GCDFP-15 stain?

It can be used in differentiating primary and secondary extramammary Paget disease
It is an independent prognostic marker for breast cancers
It is the most sensitive marker for metastatic breast cancer
It is uniformly positive in all apocrine lesions of the breast
It is positive in malignant but not benign salivary gland neoplasms

Board review style answer #1

A. It can be used in differentiating primary and secondary extramammary Paget disease. GCDFP-15 is positive in primary extramammary Paget disease while negative in secondary extramammary Paget disease (Arch Pathol Lab Med 1998;122:1077). Answer B is incorrect because GCDFP-15 does not show independent prognostic power over hormone markers. Answer E is incorrect because positive staining can be seen in pleomorphic adenomas. Answer D is incorrect because the positive rate of GCDFP-15 in apocrine lesions of the breast is just over 50%. Answer C is incorrect because GATA3 and TRPS1 are superior in sensitivity to GCDFP-15 for metastatic breast cancer.

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Reference: Gross cystic disease fluid protein 15 (GCDFP-15)

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