GATA3

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Definition: GATA3 is a zinc-finger transcription factor (ZFNs), which is expressed in various normal and neoplastic tissues.

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 carcinomas and urothelial carcinoma but also for renal tumors and germ cell tumors, mesotheliomas , and paragangliomas.

Image

 GATA3 expression in a metastatic urothelial carcinoma to the ovary

• https://twitter.com/ESadimin/status/718450304493219840

 GATA3 expression in a metastatic lobular carcinoma in colon polyp

• https://twitter.com/bestpathologist/status/715258389425557504
• https://twitter.com/Andres_Matoso/status/1228443971745144833

 Metaplastic carcinoma of the breast (GATA3+ , p63+ ) with chondroid matrix and osteoclast-like giant cells (CD68+)

• https://twitter.com/JustineVarinot/status/832230222703497217

Pathology

 GATA3 mutations cause HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome (Endocr J 2011;58:117)

 GATA3 expression in 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.
• http://dx.doi.org/10.1016/j.anndiagpath.2016.09.011

Expression in normal cells

 GATA3 expression in squamous epithelium / squamous epithelia

• https://twitter.com/Konzult_/status/863897666148855810

 GATA3 expression in breast epithelium

• Luminal marker for breast epithelium

 GATA3 expression in mature T lymphocytes

• master regulator of helper T cells type 2

Diagnostic IHC use - Expression in tumors

 GATA3 expression in breast carcinomas (72%)
 GATA3 expression in urothelial carcinoma (67%)
 GATA3 expression in collecting duct carcinoma of the kidney ( CDCK )
 GATA3 expression in peripheral T cell lymphoma NOS (30%)
 +/- GATA3 expression in endometrial carcinoma

 GATA3 expression in mesotheliomas / mesothelioma

• diagnostic between sarcomatoid mesothelioma / desmoplastic mesothelioma and sarcomatoid carcinoma of the lung
• The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin.
• GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to stain other types of tumors including some mesotheliomas.
• Strong diffuse staining for GATA3 favors a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma over metastatic sarcomatoid carcinoma of the lung.
• Conversely, complete absence of GATA-3 staining is evidence against a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma.

IHC - No expression

 mammary myoepithelial cells

Molecular pathology

 germline mutations of GATA3 in :

• HDR syndrome
• hypoparathyroidism , sensorineural deafness , and renal disease syndrome (Barakat syndrome ) (MIM.146255)

 GATA3 somatic mutations in :

• mammary carcinomas (15361840)

Immunochemistry

 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

 Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung. (22982890)

• 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.

 paragangliomas

• GATA3 expression in bladder paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. (23599157)

Open references

 GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors.
Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z.
Am J Surg Pathol. 2014 Jan;38(1):13-22. doi : 10.1097/PAS.0b013e3182a0218f
PMID: 24145643

 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]

Paywall References

 GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung.
Berg KB, Churg A.
Am J Surg Pathol. 2017 Jun 13. doi : 10.1097/PAS.0000000000000825
PMID: 28614203

 GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.
Davis DG, Siddiqui MT, Oprea-Ilies G, Stevens K, Osunkoya AO, Cohen C, Li XB.
Hum Pathol. 2016 Jan;47(1):26-31. doi : 10.1016/j.humpath.2015.09.015. Epub 2015 Sep 30
PMID: 26527523

 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