[815] Utility of Gata3 in the Diagnosis of Urothelial Carcinoma

Alex Chang, Ali Amin, Peter Illei, Edward Gabrielson, Jonathan I Epstein. The Johns Hopkins Hospital, Baltimore

Background: Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. In men, UC must be differentiated from high-grade prostatic adenocarcinoma and spread from an anal squamous cell carcinoma (SCC).
Design: Immunohistochemistry for GATA3, thrombomodulin, and uroplakin III was performed on a tissue microarray (TMA) containing cores from 35 radical cystectomy specimens with invasive high-grade UC. A TMA with 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas and tissue sections from 15 cases of invasive anal SCC were stained with GATA3. Additionally, tissue sections from 15 cases of pulmonary metastases of UC and a TMA with 25 cases of pulmonary SCC and 5 cases of non-small cell carcinomas of the lung with squamous features were stained with GATA3.
Results: Of the 28 GATA3 positive UCs, 25 (89%) cases showed moderate or strong staining, while 3 (11%) cases had weak staining. All positive GATA3 staining was non-focal with at least 20% of the tumor cells being positive. Of the 7 cases that failed to express GATA3, 5 were positive for thrombomodulin and/or Uroplakin III, while 2 cases were negative for all 3 markers. None of 38 high grade prostatic adenocarcinomas were 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 cases showed focal weak staining and 1 case showed focal moderate staining. Weak staining was also rarely observed in the benign anal squamous epithelium. Twelve (80%) of the metastatic UC 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 SCC or non-small cell carcinomas with squamous features were GATA3 positive.

	Positive Cases	Negative Cases
GATA3	28 (80%)	7 (20%)
Thrombomodulin	22 (63%)	13 (37%)
Uroplakin III	21 (60%)	14 (40%)

Conclusions: GATA3 is a sensitive immunohistochemical marker for UC and positive staining in UC is typically non-focal and moderate or strong in intensity. In male patients, when excluding high-grade prostatic adenocarcinoma, GATA3 is a specific marker. Caution must be taken as rare cases of anal SCC can be GATA3 positive, however this staining, unlike staining in UC, tends to be focal and weak. GATA3 is also a useful marker when diagnosing metastatic UC. Studies assessing GATA3 expression in invasive cervical SCC will be performed.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 84, Tuesday Afternoon