GATA binding protein 3 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, Yi Li, Qi Yang, Loralee A. McMahon, Nilda Gonzalez-Roibon, David G. Hicks, David Tacha, George J. Netto

Research output: Contribution to journalArticle

Abstract

Although GATA binding protein 3, a zinc finger transcription factor and an estrogen receptor-regulated gene, has recently been suggested as a marker for urothelium, prognostic significance of GATA binding protein 3 expression in bladder tumor remains unclear. We immunohistochemically stained for GATA binding protein 3 in urothelial neoplasm and matched nonneoplastic bladder tissue specimens. GATA binding protein 3 was positive in 125 (86%; 13 [9%] weak, 44 [30%] moderate, and 68 [47%] strong) of 145 bladder tumors, which was significantly lower than in benign urothelium (104/106 [98%]; 3 [3%] weak, 30 [28%] moderate, and 71 [67%] strong) (P = .001). Fifty (98%) of 51 low-grade tumors were GATA binding protein 3 positive, whereas 75 (80%) of 94 high-grade carcinomas were GATA binding protein 3 positive (P =.002). Similarly, 78 (98%) of 80 non-muscle-invasive tumors expressed the GATA binding protein 3, compared with 47 (72%) of 65 muscle-invasive tumors (P <.001). Conversely, among 68 cases treated with cystectomy, significantly lower expression of GATA binding protein 3 was found in pN0 tumors (32/47 [68%]) than in node-positive tumors (20/21 [95%]) (P =.027). Kaplan-Meier and log-rank tests further revealed that overall positivity (P =.048) or strong positivity (P =.025) of GATA binding protein 3 correlated with progression of muscle-invasive tumors. Multivariate analysis identified high GATA binding protein 3 expression as a strong prognosticator for progression (P =.052) and cancer-specific survival (P =.040) of muscle-invasive tumors. Moreover, there were significant correlations between GATA binding protein 3 expression vs androgen receptor overexpression, estrogen receptor α overexpression, or loss of estrogen receptor β expression. Thus, compared with benign urothelium, a significant decrease in the expression of GATA binding protein 3 in urothelial neoplasms was seen. Loss of GATA binding protein 3 was associated with high-grade and/or muscle-invasive tumors, whereas strong expression was an independent predictor of poor prognosis.

Original languageEnglish (US)
Pages (from-to)2033-2040
Number of pages8
JournalHuman pathology
Volume43
Issue number11
DOIs
StatePublished - Nov 1 2012

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Keywords

  • Bladder tumor
  • GATA3
  • Immunohistochemistry
  • Prognosis
  • Sex hormone receptors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Miyamoto, H., Izumi, K., Yao, J. L., Li, Y., Yang, Q., McMahon, L. A., Gonzalez-Roibon, N., Hicks, D. G., Tacha, D., & Netto, G. J. (2012). GATA binding protein 3 is down-regulated in bladder cancer yet strong expression is an independent predictor of poor prognosis in invasive tumor. Human pathology, 43(11), 2033-2040. https://doi.org/10.1016/j.humpath.2012.02.011