Carbonic anhydrase IX in bladder cancer

• Published in: Cancer Vol. 115; no. 7; pp. 1448 - 1458
• Main Authors: Klatte, Tobias, Seligson, David B., Rao, Jian Yu, Yu, Hong, de Martino, Michela, Kawaoka, Kelly, Wong, Steven G., Belldegrun, Arie S., Pantuck, Allan J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2009
• Subjects: bladder cancer; carbonic anhydrase IX; molecular marker; prognosis
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24163

BACKGROUND: The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2009. © 2009 American Cancer Society. The authors investigated carbonic anhydrase IX (CAIX) expression in 340 patients with urothelial carcinoma of the bladder. CAIX was expressed differentially in noninvasive versus invasive bladder cancer, in low‐grade versus high‐grade bladder cancer, and in the primary tumor versus metastasis. CAIX was identified as a strong predictor of recurrence, progression, and overall survival in patients with bladder cancer, and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The results suggested a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer.