title: GATA binding protein 3 is down-regulated in bladder cancer yet strong expression is an independent predictor of poor prognosis in invasive tumor.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. hiroshi_miyamoto@urmc.rochester.edu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Izumi
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Yao
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Loralee A
authors.initials: LA
authors.lastname: McMahon
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.forename: David
authors.initials: D
authors.lastname: Tacha
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015653:Cystectomy; D015536:Down-Regulation; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D014481:United States / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human