Testing for urinary hyaluronate improves detection and grading of transitional cell carcinoma

• Published in: Urologic oncology Vol. 29; no. 6; pp. 710 - 715
• Main Authors: Passerotti, Carlo C., M.D., Ph.D, Srougi, Miguel, M.D., Ph.D, Bomfim, Alexandre C., M.D, Martins, Joao Roberto M., M.D., Ph.D, Leite, Katia R.M., M.D., Ph.D, dos Reis, Sabrina T., Ph.D, Sampaio, Lucia O., Ph.D, Ortiz, Valdemar, M.D, Dietrich, Carl P., M.D, Nader, Helena B., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-11-2011; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Area Under Curve; Biological and medical sciences; Biomarkers, Tumor - urine; Carcinoma, Transitional Cell - diagnosis; Carcinoma, Transitional Cell - urine; Enzyme-Linked Immunosorbent Assay; Female; Human bladder neoplasms; Humans; Hyaluronic Acid - urine; Male; Medical sciences; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nephrology. Urinary tract diseases; ROC Curve; Transitional cell carcinoma; Tumor marker; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - urine; Urinary hyaluronan; Urinary tract. Prostate gland; Urology; Tumor marker; Transitional cell carcinoma; Urinary hyaluronan; Human bladder neoplasms; Histological grading; Human; Urine; Nephrology; Urinary system disease; Tumoral marker; Urinary tract disease; Malignant tumor; Medical screening; Bladder tumor; Urology; Cancerology; Healing agent; Glycosaminoglycan; Bladder disease; Antirheumatic agent; Diagnosis; Hyaluronic acid; Cancer
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2009.10.006

Abstract Objective The purpose of this study is to establish a method for the diagnosis and grading of transitional cell carcinoma (TCC), which is responsible for 90% of bladder tumors, using a recently developed ultrasensitive assay for the measurement of hyaluronan (HA). Materials and methods Urine samples were collected prior to surgery (cystoscopy, transurethral resection for bladder cancer (TURBT), and cystectomy) in 350 patients. After the procedure, pathologic examination revealed that 160 patients had TCC. HA was measured directly in the urine by a noncompetitive enzyme-linked immunosorbent assay (ELISA)-like fluorometric assay. Using the receiver operator characteristic curve (ROC), t -test, Dunn test, Kruskal-Wallis test, and Mann-Whitney test, we evaluated the differences between groups (those with TCC vs. those without TCC). Results By analyzing the ROC curve, we chose a urinary HA cutoff value of 13.0 μg/l for indicating risk of TCC. Using the value this of 13.0 μg/l, we found that this test had an overall sensitivity of 82.3% and an overall specificity of 81.2%. The positive predictive value of this assay was 78.9%, the negative predictive negative value was 84.2%, and the predictive accuracy was 81.7%. Logistic regression analysis revealed that every 1 μg/l increase in HA increased a patient's likelihood of having TCC by 3.9%. The sensitivity of this test to detect superficial tumors was 76.6%, whereas its sensitivity for detecting invasive tumors was 94.6%. The urinary HA excretion of patients with TCC, classified according to the TNM staging system and the World Health Organization (WHO) grading system, were compared, and a significant difference was observed between the HA levels of patients with superficial tumors compared with invasive tumors ( P = 0.005) as well as between patients with low- vs. high-grade carcinomas ( P < 0.001). Patients with urinary HA levels >35 μg/l had a 4.63 times increased risk of having an aggressive, invasive, high grade tumor ( P = 0.005). Conclusions Our results support the postulate that urinary HA may be used as a tumor marker to aid in the diagnosis and grading of TCC. Additionally, more invasive tumors produce and release more HA in urine than superficial tumors, thus higher HA levels indicate more aggressive disease.