The detection of high-grade bladder tumors prior to invasion is crucial for a good prognosis. We recently found that the levels of hyaluronic acid (HA), a glycosaminoglycan,are elevatedin the urine of bladder cancer

The detection of high-grade bladder tumors prior to invasion is crucial for a good prognosis. We recently found that the levels of hyaluronic acid (HA), a glycosaminoglycan,are elevatedin the urine of bladder cancer patients, and small angiogenic HA fragments are present in the urine of high-grade bladder cancer patients. Hyaluronidase is an enzyme that degrades HA into small angiogenic fragments. We compared the urinary hyaluronidase levels of normal individuals and patients with bladder cancer or other genitourinary conditions, using a substrate (HA)-gel technique and an ELISA-like assay. Among the 139 specimens analyzed, the urinary hyaluronidase levels in patients with G2/G3 tumors (33.4 ±4.5 milliunits/mg protein) are S—S-foldhigher than those in normal individuals (4.2 ±1.2 milliunits/mg protein) and those in patients with Gi tumors (65 ±1.7 mffliunits/mg protein) or other genitourinary conditions (7.4 ±1.4 milliunits/mg protein; P < 0.001). Urinary hyalu ronidase measurement shows a sensitivity of 100% and a specificity of 88.8% to detecthigh-gradebladder(G2/G3) tumors.Thusurinary hya luronidase measurement is a simple, noninvasive yet highly specific and sensitive method for high-grade bladder cancer detection. The increase in urinary hyaluronidase levels is due to the secretion of a tumor-associated hyaluronidase into the urine because the hyaluronidase levels in G21G3 tumor tissues are also higher (6—7-fold) than those in normal bladder and Gi tumor tissues (P < 0.001). The bladder tumor-associated hyaluroni dazeactivity is distinct from other hyaluronidases,hasa pH opthnum of 4.3, and is attributed to two proteins with molecular massesof6S kD (p65) and 55 kD (p55).