Tumour-associated protein carbonic anhydrase IX (CA IX) has two major forms. One is a cell-associated, transmembrane protein seen on Western blots as a twin band of 54/58 kDa, expressed in gastric mucosa and in several types of cancer. The other is a soluble protein s-CA IX of 50/54 kDa, which is released into the culture medium or into the body fluids, most likely by proteolytic cleavage of the extracellular part from transmembrane and intracellular sequences. While TC media of CA IX-positive tumour cell lines or shortterm cultures of tumour explants contain a relatively high concentration of s-CA IX (20 -50 ng ml À1 ), the level of this antigen in blood serum and urine of renal clear cell carcinoma patients is about 1000 Â lower. The concentration of CA IX in the blood and in urine varies within wide limits and there is no obvious correlation with tumour size. After nephrectomy, s-CA IX is cleared from the blood within a few days. Only an extremely low concentration of CA IX was detectable in the sera and in urine of control individuals.

We investigated the expression of cell-associated CAIX protein in histological sections of the transitional cell carcinoma (TCC) of the urinary tract and of the soluble form of CAIX (s-CAIX) shed by the tumor into the serum and urine of TCC patients. A total of 23 patients with histologically confirmed TCC or squamous cell carcinoma (SCC) were enrolled in the pilot study. Sixteen healthy individuals served as controls. Membrane-bound CAIX was present in the tumor cells near the endoluminal surface. Necrosis was observed in only 4 samples. Using Western blots, s-CAIX concentrated from urine was visualized as a double band at 50 and 54 kDa. In most cases, the presence of s-CAIX in the urine correlated with CAIX expression in the tumor. On the other hand, s-CAIX did not exceed the normal level in the serum of TCC patients. Urine from patients with TCC of the urinary bladder and renal pelvis contained s-CAIX, allowing the detection of tumors in approximately 70% of the patients. Moreover, two additional patients with suspected, but unconfirmed bladder tumor, with s-CAIX detected in urine, developed tumors identified as TCC within six months. We suggest that after a simple, rapid and sensitive test, monitoring s-CAIX levels in urine will be developed, it may be useful for early detection of relapse in patients following transurethral tumor resection.

9. Bleumer I, Knuth A, Oosterwijk E, et al: A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients. Br J Cancer 90:985-990, 2004 10. Bleumer I, Oosterwijk E, Oosterwijk-Wakka JC, et al: A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma. J Urol 175:57-62, 2006 11. Steffens MG, Boerman OC, de Mulder PH, et al: Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131 I-labeled chimeric monoclonal antibody G250. Clin Cancer Res 5:3268s-3274s, 1999 (suppl) 12. Brouwers AH, Mulders PF, de Mulder PH, et al: Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131 I-cG250 in patients with metastasized clear cell renal cell carcinoma. J Clin Oncol 23:6540-6548, 2005 13. Brouwers AH, Dorr U, Lang O, et al: 131 I-cG250 monoclonal antibody immunoscintigraphy versus [ 18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: A comparative study. Nucl Med Commun 23:229-236, 2002 14. Brouwers AH, Buijs WCAM, Oosterwijk E, et al: Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with

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Preoperative somatic symptoms and performance status in patients with RCC provide readily available prognostic information in addition to tumour size, stage and grade.