Tuesday 24 May 2005
GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T-lymphocytes. It has been suggested useful in the evaluation of mammary or urothelial origin or metastatic carcinomas.
GATA3 is a useful marker in characterization not only mammary and urothelial but also for renal and germ cell tumors, mesotheliomas, and paragangliomas.
GATA3 expression in a metastatic lobular carcinoma in colon polyp
GATA3 mutations cause HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome (Endocr J 2011;58:117)
invasive breast cancer
- Low GATA3 immunoexpression may be poor prognostic factor for invasive breast cancer (Hum Pathol 2010;41:1794)
- GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas.
- GATA3 was significantly more sensitive than traditional marker GCDFP15 and mammaglobin (MGB ).
- GATA3 expression did not show the same sensitivity for the clinically useful groups of breast cancer.
- GATA3 expression is positively correlated with ER-positive, PR-positive, and HER2-positive carcinomas.
- The matched primary and metastatic tumor expression of GATA3 show good coincidence.
- It has been proposed the careful selection of GATA3 for identifying hormone receptor-negativity of breast cancer, especially in the case of triple-negative breast cancer.
Expression in normal cells
- Luminal marker for breast epithelium
mature T lymphocytes
- master regulator of helper T cells type 2
IHC use - Expression in tumors
breast carcinomas (72%)
urothelial carcinoma (67%)
collecting duct carcinoma of the kidney ( CDCK )
peripheral T cell lymphoma NOS (30%)
+/- endometrial carcinoma
IHC - No expression
mammary myoepithelial cells
germline mutations of GATA3 in :
- HDR syndrome
- hypoparathyroidism , sensorineural deafness , and renal disease syndrome ( Barakat syndrome ) (MIM.146255)
somatic mutations in :
GATA3 has been recognized as a promising marker for primary urothelial carcinoma (UC), consistently showing higher expression levels than urothelial markers thrombomodulin and uroplakin III .
- Specificity of GATA3 calculated on the basis of morphologic and immunophenotypic UC mimics from lung, cervix, head and neck is 92%.
- Some findings demonstrate high sensitivity and specificity of the GATA3 diagnostic marker, with not only maintained but increased expression in regional metastases.
- doi : 10.1097/PAS 0b013e31829e2525
- Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult.
- The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC.
- In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC.
- GATA3 IHC is a sensitive marker for UC, and positive staining in UC is typically nonfocal and moderate or strong in intensity.
- GATA3 is also highly specific in excluding high-grade prostate adenocarcinoma.
- Although some cervical and anal SCCs can be GATA3 positive, unlike in UC, staining is more commonly focal and weak.
- GATA3 is also a useful maker when diagnosing metastatic UC to the lung.
- GATA3 expression in bladder paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. (23599157)
GATA 3 – A MULTISPECIFIC BUT POTENTIALLY USEFUL MARKER IN SURGICAL PATHOLOGY 2014. doi : 10.1097/PAS.0b013e3182a0218f
GATA3 expression in paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. So JS, Epstein JI. Mod Pathol. 2013 Oct;26(10):1365-70. doi : 10.1038/modpathol.2013.76 PMID: 23599157 [Free]
Differential expression of GATA-3 in urothelial carcinoma variants. Liang Y, Heitzman J, Kamat AM, Dinney CP, Czerniak B, Guo CC. Hum Pathol. 2014 Jul;45(7):1466-72. doi : 10.1016/j.humpath.2014.02.023 PMID: 24745616
Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung. Chang A, Amin A, Gabrielson E, Illei P, Roden RB, Sharma R, Epstein JI. Am J Surg Pathol. 2012 Oct;36(10):1472-6. doi : 10.1097/PAS.0b013e318260cde7 PMID: 22982890
Ali A, Christie PT, Grigorieva IV, Harding B, Van Esch H, Ahmed SF, Bitner-Glindzicz M, Blind E, Bloch C, Christin P, Clayton P, Gecz J, Gilbert-Dussardier B, Guillen-Navarro E, Hackett A, Halac I, Hendy GN, Lalloo F, Mache CJ, Mughal Z, Ong AC, Rinat C, Shaw N, Smithson SF, Tolmie J, Weill J, Nesbit MA, Thakker RV. Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding by the GATA3 transcription factor. Hum Mol Genet. 2007 Feb 1;16(3):265-75. PMID: 17210674