Tuesday 24 May 2005
GATA3 mutations cause HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome (Endocr J 2011;58:117)
Expression in normal cells
- Luminal marker for breast epithelium
mature T lymphocytes
- master regulator of helper T cells type 2
Expression in tumors
urothelial carcinoma (67%)
collecting duct carcinoma of the kidney ( CDCK )
breast carcinomas (72%)
peripheral T cell lymphoma NOS (30%)
+/- endometrial carcinoma
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)
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