TUMOR-DERIVED HYALURONIDASE - A DIAGNOSTIC URINE MARKER FOR HIGH-GRADE BLADDER-CANCER

The detection of high-grade bladder tumors prior to invasion is crucia l for a good prognosis, We recently found that the levels of hyaluroni c acid (HA), a glycosaminoglycan, are elevated in 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 enzy me that degrades HA into small angiogenic fragments, We compared the u rinary hyaluronidase levels of normal individuals and patients with bl adder cancer or other genitourinary conditions, using a substrate (HA) -gel technique and an ELISA-like assay, Among the 139 specimens analyz ed, the urinary hyaluronidase levels in patients with G2/G3 tumors (33 .4 +/- 4.5 milliunits/mg protein) are 5-8-fold higher than those in no rmal individuals (4.2 +/- 1.2 milliunits/mg protein) and those in pati ents with G1 tumors (6.5 +/- 1.7 milliunits/mg protein) or other genit ourinary conditions (7.4 +/- 1.4 milliunits/mg protein; P < 0.001), Ur inary hyaluronidase measurement shows a sensitivity of 100% and a spec ificity of 88.8% to detect high-grade bladder (G2/G3) tumors, Thus uri nary hyaluronidase measurement is a simple, noninvasive yet highly spe cific and sensitive method for high-grade bladder cancer detection, Th e increase in urinary hyaluronidase levels is due to the secretion of a tumor-associated hyaluronidase into the urine because the hyaluronid ase levels in G2/G3 tumor tissues are also higher (6-7-fold) than thos e in normal bladder and G1 tumor tissues (P < 0.001), The bladder tumo r-associated hyaluronidase activity is distinct from other hyaluronida ses, has a pH optimum of 4.3, and is attributed to two proteins with m olecular masses of 65 kD (p65) and 55 kD (p55).