Pham H T, Block N L, Lokeshwar V B
Department of Urology, University of Miami School of Medicine, Florida 33101, USA.
Cancer Res. 1997 Feb 15;57(4):778-83.
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 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 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 5-8-fold higher than those in normal individuals (4.2 +/- 1.2 milliunits/mg protein) and those in patients with G1 tumors (6.5 +/- 1.7 milliunits/mg protein) or other genitourinary conditions (7.4 +/- 1.4 milliunits/mg protein; P < 0.001). Urinary hyaluronidase measurement shows a sensitivity of 100% and a specificity of 88.8% to detect high-grade bladder (G2/G3) tumors. Thus urinary hyaluronidase 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 G2/G3 tumor tissues are also higher (6-7-fold) than those in normal bladder and G1 tumor tissues (P < 0.001). The bladder tumor-associated hyaluronidase activity is distinct from other hyaluronidases, has a pH optimum of 4.3, and is attributed to two proteins with molecular masses of 65 kD (p65) and 55 kD (p55).
在浸润前检测高级别膀胱肿瘤对于良好的预后至关重要。我们最近发现，膀胱癌患者尿液中糖胺聚糖透明质酸（HA）的水平升高，并且高级别膀胱癌患者尿液中存在小的血管生成性HA片段。透明质酸酶是一种将HA降解为小的血管生成性片段的酶。我们使用底物（HA）-凝胶技术和类似ELISA的检测方法，比较了正常个体以及膀胱癌或其他泌尿生殖系统疾病患者的尿透明质酸酶水平。在分析的139份标本中，G2/G3肿瘤患者的尿透明质酸酶水平（33.4±4.5毫单位/毫克蛋白质）比正常个体（4.2±1.2毫单位/毫克蛋白质）以及G1肿瘤患者（6.5±1.7毫单位/毫克蛋白质）或其他泌尿生殖系统疾病患者（7.4±1.4毫单位/毫克蛋白质）高5至8倍（P<0.001）。尿透明质酸酶检测对检测高级别膀胱（G2/G3）肿瘤的敏感性为100%，特异性为88.8%。因此，尿透明质酸酶检测是一种简单、无创但高度特异且敏感的高级别膀胱癌检测方法。尿透明质酸酶水平的升高是由于肿瘤相关透明质酸酶分泌到尿液中，因为G2/G3肿瘤组织中的透明质酸酶水平也比正常膀胱和G1肿瘤组织高（6至7倍）（P<0.001）。膀胱肿瘤相关透明质酸酶活性与其他透明质酸酶不同，最适pH为4.3，并且归因于分子量为65 kD（p65）和55 kD（p55）的两种蛋白质。
