Gross cystic disease fluid protein 15, GCDFP-15

The gross cystic disease fluid proteins were first identified in the fluid of breast cysts and in the serum of patients with mammary carcinomas. The members of this family of proteins are named from their molecular weights in kilodaltons, the major constituents in breast cyst fluid being GCDFP-15, GCDFP-24 (also known as apolipoprotien-D) and GCDFP-44 (also known as zinc alpha2-glycoprotein)⁷. GCDFP-15 is the most reproducibly present in breast carcinomas: this protein is induced by prolactin.

Immunohistochemical expression

Non-neoplastic serous salivary gland acini, bronchial serous glands, seminal vesicles and apocrine skin adnexa are immunoreactive⁴. Renal tubules, ovarian surface epithelium and urothelium are negative⁴. Staining is cytoplasmic, often with paranuclear enhancement in mammary carcinomas⁴. There is concordance between the immunoreactivity of primary breast carcinomas and their metastases⁴.

	Breast carcinoma	62-77% of cases1, 10/14 (breast carcinomas metastatic to ovary)3, 4/295, 80/1076
	ductal carcinoma	71/1192, 62/824
	lobular carcinoma	9/102, 8/154
	ductal carcinoma in situ	5/64
	mucinous carcinoma	1/24
	Salivary gland tumours
	acinic cell tumour	5/124
	mucoepidermoid carcinoma	1/64
	adenoid cystic carcinoma	0/54
	adenocarcinoma, NOS	5/334
	Skin adnexal tumours	positive1
	eccrine carcinoma	1/164
	Vulval Paget's disease	9/9 (6 in situ and 3 invasive)4
	Prostatic carcinomas	4/404
	Pulmonary carcinomas	2/352
	Gastric carcinomas	1/392
	Colonic carcinoma	0/252, 0/946
	Pancreatic carcinoma	0/292
	Ovarian carcinoma	0/292, 0/323, 0/866, 1/26 (epithelial carcinomas)4
	Renal carcinomas	0/452, 1/294
	Bladder carcinomas	1/674
	Other carcinomas	usually negative1
	Various non-mammary carcinomas	5%4

Positivity for GCDFP-15 occurs in breast carcinomas that are negative for ER or PR⁴:

		ER		PR
		positive	negative	positive	negative
GCDFP-15	positive	12	11	8	8
	negative	4	10	2	7

One study compared the expresion of the three major gross cystic disease fluid proteins in DCIS⁷:

		GCDFP-15	GCDFP-24	GCDFP-44
	well-differentiated	5/13	3/13	5/13
	moderately differentiated	11/19	9/19	11/19
	poorly differentiated	8/25	8/25	6/25
	total	24/57	20/57	22/57
	with apocrine differentiation	7/9	5/9	6/9

	Malignant pleural epithelioid mesothelioma	0/218
	Malignant peritoneal epithelioid mesothelioma	0/208
	Peripheral pulmonary adenocarcinoma involving pleura	0/238
	Serous surface papillary adenocarcinoma of peritoneum	0/108
	Breast carcinoma metastatic to pleura	7/108

Diagnostic utility

• Identification of carcinoma as metastatic from breast.

References

¹Lerwill, M. F. (2004). "Current practical applications of diagnostic immunohistochemistry in breast pathology." Am J Surg Pathol 28(8): 1076-91.

²Kaufmann, O., T. Deidesheimer, et al. (1996). "Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites." Histopathology 29(3): 233-40.

³Monteagudo, C., M. J. Merino, et al. (1991). "Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary." Hum Pathol 22(4): 368-72.

⁴Wick, M. R., T. J. Lillemoe, et al. (1989). "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 20(3): 281-7.

⁵Lee, B. H., J. L. Hecht, et al. (2002). "WT1, estrogen receptor, and progesterone receptor as markers for breast or ovarian primary sites in metastatic adenocarcinoma to body fluids." Am J Clin Pathol 117(5): 745-50.

⁶Lagendijk, J. H., H. Mullink, et al. (1999). "Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach." J Clin Pathol 52(4): 283-90.

⁷ Selim AA, El-Ayat G,Wells CA Immunohistochemical localization of gross cystic disease fluid protein-15, -24 and -44 in ductal carcinoma in situ of the breast: relationship to the degree of differentiation. Histopathology 2001; 39:198-202

⁸ Wick MR, Mills SE,Swanson PE Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces. Am J Clin Pathol 1990; 94:18-26

This page last revised 19.8.2005.

©SMUHT/PW Bishop