title: Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.
abstract: 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. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely observed in the benign anal squamous epithelium. Of the 31 uterine cervical carcinomas, 6 (19%) showed weak GATA3 staining (3 nonfocal and 3 focal), and 2 (6%) demonstrated focal moderate staining. Twelve (80%) of the metastatic UCs to the lung were positive for GATA3, with 11 cases showing diffuse moderate or strong staining and 1 case showing focal moderate staining. None of the pulmonary SCCs or non-small cell carcinomas with squamous features was GATA3 positive. 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.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Chang
authors.forename: Ali
authors.initials: A
authors.lastname: Amin
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
authors.forename: Peter
authors.initials: P
authors.lastname: Illei
authors.forename: Richard B
authors.initials: RB
authors.lastname: Roden
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism; D046888:Tissue Array Analysis; D014565:Urogenital Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human