Carbonic Anhydrase IX in Bladder Cancer : A Diagnostic, Prognostic, and Therapeutic Molecular Marker

• Published in: Cancer Vol. 115; no. 7; pp. 1448 - 1458
• Main Authors: KLATTE, Tobias, SELIGSON, David B, JIAN YU RAO, HONG YU, DE MARTINO, Michela, KAWAOKA, Kelly, WONG, Steven G, BELLDEGRUN, Arie S, PANTUCK, Allan J
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.04.2009
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - analysis; Biological and medical sciences; Biomarkers, Tumor - analysis; Carbonic Anhydrase IX; Carbonic Anhydrases - analysis; Disease Progression; Female; Follow-Up Studies; Humans; Male; Medical sciences; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis - diagnosis; Nephrology. Urinary tract diseases; Prognosis; Recurrence; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urinary tract. Prostate gland; Urothelium - chemistry; Urinary system disease; Prognosis; Genetic marker; Molecular diagnostic; Enzyme; Lyases; Urinary tract disease; Malignant tumor; Molecular marker; Bladder cancer; Cancerology; Treatment; carbonic anhydrase IX; Bladder disease; Carbonate dehydratase; Carbon-oxygen lyases; Cancer; Hydro-lyases
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24163

The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder. A tissue microarray was constructed that contained 724 tissue samples from 340 patients. Immunohistochemical staining was performed using the antibody MN-75, the percentage of positive cells was evaluated, and their association with tumor (T) classification, grade, and survival was assessed. All normal urothelial tissue samples were negative for CAIX expression, whereas 71% of bladder cancers expressed CAIX. CAIX expression was higher in noninvasive (Ta) versus invasive (T1-T4) tumors (P < .001), in low-grade versus high-grade bladder cancer (P < .001), and in metastases versus the corresponding primary tumor (P = .032). For patients with nonmuscle invasive carcinoma who underwent transurethral resection (TUR), higher CAIX expression was associated with poorer recurrence-free survival (P = .001). In addition, for patients with T1 tumors who underwent TUR, higher CAIX expression conveyed a 6.5-fold higher risk of progression into muscle-invasive disease (P = .006). In patients who underwent cystectomy, higher CAIX expression was associated with worse overall survival (P = .003). Multivariate Cox models revealed that CAIX expression was the strongest, independent prognostic factor of recurrence-free survival (hazard ratio, 2.29; P = .001) and overall survival (hazard ratio, 1.9; P < .001). CAIX was expressed differentially in noninvasive versus invasive tumors, in low-grade versus high-grade bladder cancer, and in primary tumors versus metastases. The current results indicated that CAIX is a strong predictor of recurrence, progression, and overall survival of patients with bladder cancer; and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The data suggest a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer.