GATA3 Is Down-Regulated in Bladder Cancer yet Strong Expression Is an Independent Predictor of Poor Prognosis in Invasive Tumor
Hiroshi Miyamoto, Koji Izumi, Jorge L Yao, Qi Yang, Loralee A McMahon, Nilda Gonzalez-Roibon, Alcides Chaux, David G Hicks, George J Netto, David Tacha. University of Rochester, Rochester, NY; Johns Hopkins Medical Institution, Baltimore, MD; Biocare Medical, Concord, CA
Background: GATA3, a zinc finger transcription factor and an estrogen receptor (ER)-regulated gene, plays a critical role in breast tumorigenesis. GATA3 has recently been suggested as a marker for urothelium/urothelial neoplasm. However, little is known about the prognostic significance of GATA3 expression and its correlation with ER expression in bladder tumor.
Design: We immunohistochemically stained for GATA3 in 145 bladder tumor specimens and matched 106 non-neoplastic bladder tissues for which the expression levels of androgen receptor (AR), ERα, and ERβ had been assessed. We then evaluated the association between GATA3 expression and clinicopathologic features available for our patient cohort.
Results: GATA3 was positive in 125/145 [86%; 13 (9%) weak, 44 (30%) moderate, and 68 (47%) strong] urothelial neoplasms, which was significantly lower than in benign urothelium [104/106 (98%); 3 (3%) weak, 30 (28%) moderate, and 71 (67%) strong] (P=0.001). Fifty (98%) of 51 low-grade tumors were GATA3-positive, whereas 75 (77%) of 98 high-grade carcinomas were GATA3-positive (P=0.001). Similarly, 78 (98%) of 80 non-muscle-invasive tumors expressed GATA3, compared with 47 (72%) of 65 muscle-invasive tumors (P<0.001). In contrast, among 68 cases treated with cystectomy, significantly lower expression of GATA3 was found in pN0 tumors [32/47 (68%)] than in node-positive tumors [20/21 (95%)] (P=0.027). There was no significant difference in the GATA3 expression pattern between bladder tumors from male vs. female patients. Kaplan-Meier and log-rank tests further revealed that overall positivity (P=0.049) or strong positivity (P=0.019) of GATA3 correlated with progression of muscle-invasive tumors. GATA levels were not strongly associated with prognosis in patients with low-grade and/or non-muscle-invasive tumors. Multivariate analysis identified high GATA3 expression as a strong prognosticator for progression (P=0.052) and cancer-specific survival (P=0.040) of muscle-invasive tumors. Moreover, there were statistically significant correlations between the expression of GATA3 vs. AR (P=0.006) or ERα (P=0.025), but not ERβ (P=0.473).
Conclusions: Compared to benign urothelium, a significant decrease in the expression of GATA3 in urothelial neoplasms was seen. Loss of GATA3 was associated with high-grade and/or muscle-invasive tumors, while strong expression was an independent predictor of poor prognosis. We also found that GATA3 co-expressed with AR and ERα in bladder tumors.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 85, Tuesday Afternoon