Original contributionGATA3 immunohistochemistry in urothelial carcinoma of the upper urinary tract as a urothelial marker and a prognosticator

SummaryImmunohistochemistry of a transcription factor, GATA3, has been widely used as a promising urothelial marker in diagnostic surgical pathology practice. However, the expression status of GATA3 in upper urinary tract urothelial carcinomas (UUTUCs) and its prognostic significance have not been fully investigated. We immunohistochemically stained for GATA3 in 99 UUTUC samples and paired nonneoplastic urothelial tissues. GATA3 was positive in 51 (51.5%; 32 [32.3%] weak, 11 [11.1%] moderate, 8 [8.1%] strong) of 99 UUTUCs, which was significantly lower than in benign urothelium (79 [96.3%] of 82; 33 [40.2%] weak, 35 [42.7%] moderate, 11 [13.4%] strong; P < .001). However, there were no statistically significant associations between GATA3 expression and tumor grade, pT stage, lymph node involvement, or distant metastasis. Meanwhile, the rate of GATA3 positivity was significantly higher (P = .004) in ureteral tumors (66.0%) than in renal pelvic tumors (35.6%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity was significantly associated with lower recurrence-free survival (P = .037 for all cases, P = .026 for muscle-invasive tumors) and cancer-specific survival (P = .007 for all cases, P = .012 for muscle-invasive tumors, P = .035 for cases with adjuvant chemotherapy) rates. Multivariate analysis further identified strong correlations of GATA3 expression with tumor progression (all cases: hazard ratio [HR], 0.479 [95% confidence interval {CI}, 0.229-1.003; P = .051]; muscle-invasive tumors: HR, 0.387 [95% CI, 0.166-0.903; P = .028) or cancer-specific mortality (all cases: HR, 0.354 [95% CI, 0.135-0.925; P = .034]; muscle-invasive tumors: HR, 0.402 [95% CI, 0.149-1.086; P = .072]). Thus, compared with nonneoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Moreover, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. Of note was that only roughly half of high-grade and/or muscle-invasive UUTUCs were immunoreactive for GATA3.

Graphical Abstract
- GATA3 expression is down-regulated in UUTUC, compared with normal urothelium.
- Only 51.5% of UUTUCs are immunoreactive for GATA3.
- Loss of GATA3 expression in UUTUCs is an independent predictor of poor prognosis.
- GATA3 expression is correlated with AR and ERβ expression in UUTUCs.