Hyaluronic acid and HAase are intricately associated with the biology of bladder tumor angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine. In G2 and G3 bladder tumors, HA is degraded by HAase, resulting in the generation of angiogenic HA fragments, which, in turn, are secreted in urine. An elevated urinary HA level (≥500 ng/mg), indicating a positive HA test, suggests the presence of bladder cancer regardless of tumor grade. The urinary HAase levels correlate with the malignant potential of bladder cancer and are elevated (≥10 mU/mg) in the urine of patients with G2 and G3 bladder cancer. Combining the results from the HA and the HAase tests (the HA-HAase test) yields inferences, including the detection of bladder cancer and the evaluation of its grade. The overall 92% sensitivity of the HA-Aase test to detect bladder cancer is higher than the sensitivity of individual tests with little compromise in specificity. The HA-HAase test is equally sensitive for monitoring tumor recurrence. When compared with existing noninvasive tests, the HA-HAase test may be significantly less expensive and more accurate.
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