Gross cystic disease fluid protein
15, GCDFP-15, BRST-2
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 apolipoprotein-D)
and GCDFP-44 (also known as zinc alpha2-glycoprotein)7. GCDFP-15 is encoded on chromosome 7.
The protein acts as an aspartyl protease cleaving fibronectin. It also
inhibits apoptosis by T-cells. It the most reproducibly present in breast
carcinomas13: this protein is induced by prolactin
and androgen.
Immunohistochemical expression
Non-neoplastic serous salivary gland acini,
bronchial serous glands, seminal vesicles and apocrine skin adnexa (axilla,
vulva, eyelid and ear canal) are immunoreactive4,12. Within normal breast tissue, staiining
is restricted to foci of individual epithelial cells within lobules and
small ducts12. 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, 13/23(cytological
specimens)9,
24/58(this
study compared GCDFP-15 with mammaglobin)11, 4/63(by
tissue microarray: this study compared GCDFP-15 with mammaglobin)11, 14/3012,
37/8313, 54%(of 35 cases)14 |
|
ductal
carcinoma |
71/1192, 62/824,
48/9115
|
lobular
carcinoma |
9/102, 8/154,
14/2415 |
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,
0/1814 |
Pulmonary
adenocarcinomas |
2/352, 11/21110, 2/4614, 4/158(4
cases showed staining of <25% of cells: 2 of these cases ere
positive for TTF-1 and 2 were positive for Napsin-A)15 |
Pulmonary
small cell carcinoma |
0/314 |
Pulmonary
squamous cell carcinoma |
0/714,
0/391
|
Mesothelioma |
0/614 |
Oesophageal
adenocarcinoma |
0/2114 |
Oesophageal
squamous cell carcinoma |
0/714 |
Gastric
carcinomas |
1/392,
0/3414 |
Colonic
carcinoma |
0/252,
0/946, 4/4714 |
Pancreatic
carcinoma |
0/292,
1/5314 |
Ampulla
of Vater |
1/614 |
Cholangiocarcinoma |
0/1014 |
Hepatocellular
carcinoma |
0/614 |
Ovarian
carcinoma |
0/292,
0/323, 0/866,
1/26(epithelial
carcinomas)4, 2/28(1
of 18 serous, 1 of 10 mucinous)14 |
Endometrial
adenocarcinoma |
1/1014 |
Renal
carcinomas |
0/452,
1/294, 0/1514 |
Bladder
carcinomas |
1/674 |
Other
carcinomas |
usually
negative1 |
Various
non-mammary carcinomas |
5%4,
0/20(cytological
specimens)9 |
| |
|
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
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
9 Fiel
MI, Cernaianu G, Burstein DE, et al. Value of GCDFP-15 (BRST-2) as a specific
immunocytochemical marker for breast carcinoma in cytologic specimens.
Acta Cytol 1996; 40:637-41
10 Striebel
JM, Dacic S,Yousem SA. ross cystic disease fluid protein-(GCDFP-15): expression
in primary lung adenocarcinoma. Am J Surg Pathol 2008; 32:426-32
11 Bhargava
R, Beriwal S,Dabbs DJ Mammaglobin vs GCDFP-15: an immunohistologic validation
survey for sensitivity and specificity. Am J Clin Pathol 2007; 127:103-13
12 Mazoujian
G, Pinkus GS, Davis S, et al. 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; 110:105-12
13 Satoh
F, Umemura S,Osamura RY Immunohistochemical analysis of GCDFP-15 and GCDFP-24
in mammary and non-mammary tissue. Breast Cancer 2000; 7:49-55
14
Dennis
JL, Hvidsten TR, Wit EC, et al. Markers of adenocarcinoma characteristic
of the site of origin: development of a diagnostic algorithm. Clin Cancer
Res 2005; 11:3766-72 FULL TEXT
15 Yang M, Nonaka D. A study of immunohistochemical
differential expression in pulmonary and mammary carcinomas. Mod Pathol.
2010 May;23(5):654-61. (with corrections to the paper provided by
author)
This page last
revised 10.5.2010.
©SMUHT/PW
Bishop