Login to Access Video or Poster Abstract: MP71-04
Sources of Funding: None

Introduction

A transcription factor, GATA3, has been one of the most useful urothelial markers in diagnostic surgical pathology practice. However, previous studies have assessed the utility of GATA3 immunohistochemistry often in bladder specimens. Moreover, the prognostic significance of GATA3 expression in upper urinary tract urothelial carcinomas (UUTUCs) has not been fully investigated. Meanwhile, using cell line and animal models, we have demonstrated that GATA3 functions as a tumor suppressor for urothelial cancer. The current study aims to determine the expression status of GATA3 in UUTUC and its prognostic significance.

Methods

We immunohistochemically stained for GATA3 in the tissue microarrays consisting of 99 UUTUC samples and paired non-neoplastic urothelium from each case. We then evaluated the associations between GATA3 expression and clinicopathologic features available for our patient cohort.

Results

GATA3 was positive in 51 [52%; 32 (32%) weak, 11 (11%) moderate, 8 (8%) strong] of 99 UUTUCs, which was significantly lower than in benign urothelium [79 (96%) of 82; 33 (40%) weak, 35 (43%) moderate, 11 (13%) strong] (P < 0.001). Ten (67%) of 15 low-grade versus 41 (48%) of 84 high-grade UUTUCs (P = 0.266) and 20 (54%) of 37 non-muscle-invasive versus 31 (50%) of 62 muscle-invasive UUTUCs (P = 0.836) were immunoreactive for GATA3. There were also no statistically significant associations between GATA3 expression and pN status, distant metastasis, gender of the patients, or the side of UUTUC. However, the rate of GATA3 positivity was significantly higher (P = 0.004) in ureteral tumors (66%) than in renal pelvic tumors (36%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity significantly correlated with lower recurrence-free survival (P = 0.040 for all cases; P = 0.030 for muscle-invasive tumors) and cancer-specific survival (P = 0.007 for all cases; P = 0.012 for muscle-invasive tumors) rates. Multivariate analysis further identified strong correlations of GATA3 expression with cancer-specific mortality of all cases [hazard ratio (HR) = 0.399, 95% confidence interval (CI) = 0.179-0.890, P = 0.025] or muscle-invasive tumors (HR = 0.374, 95% CI = 0.169-0.831, P = 0.016).

Conclusions

Compared with non-neoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Of note was that GATA3 was immunohistochemically detected only in roughly half of high-grade and/or muscle-invasive UUTUCs. In addition, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes.

Funding

None