URINARY HYALURONIC ACID AND HYALURONIDASE: MARKERS FOR BLADDER CANCER DETECTION AND EVALUATION OF GRADE

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jan 2000URINARY HYALURONIC ACID AND HYALURONIDASE: MARKERS FOR BLADDER CANCER DETECTION AND EVALUATION OF GRADE VINATA B. LOKESHWAR, CAN ÖBEK, HENRI T. PHAM, DAVID WEI, MARVIN J. YOUNG, ROBERT C. DUNCAN, MARK S. SOLOWAY, and NORMAN L. BLOCK VINATA B. LOKESHWARVINATA B. LOKESHWAR More articles by this author , CAN ÖBEKCAN ÖBEK More articles by this author , HENRI T. PHAMHENRI T. PHAM More articles by this author , DAVID WEIDAVID WEI More articles by this author , MARVIN J. YOUNGMARVIN J. YOUNG More articles by this author , ROBERT C. DUNCANROBERT C. DUNCAN More articles by this author , MARK S. SOLOWAYMARK S. SOLOWAY More articles by this author , and NORMAN L. BLOCKNORMAN L. BLOCK More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)68050-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Specific patterns of progression and frequent recurrence of bladder tumors determine the choice of treatment, frequency of surveillance, quality of life, and ultimately, patient prognosis. The prognosis would be improved if an accurate noninvasive test was available for diagnosis. Identification of markers that function in bladder cancer progression would be helpful in designing such diagnostic tests. The glycosaminoglycan, hyaluronic acid (HA), promotes tumor metastasis. Hyaluronidase (HAase), an endoglycosidase, degrades HA into small fragments that promote angiogenesis. We have previously shown that both HA and HAase are associated with bladder cancer and may function in bladder tumor angiogenesis. In this study we examined whether urinary HA and HAase levels serve as bladder cancer markers. Materials and Methods: Among the 513 urine specimens analyzed, 261 were from transitional cell carcinoma (TCC) patients, 9 from patients with non-TCC tumors, and 243 from controls (normals, patients with other genitourinary (GU) conditions or a history of bladder cancer (HxBCa)). The urinary HA and HAase levels were measured by two ELISA-like assays that utilize a biotinylated HA binding protein for detection. These levels were normalized to total urinary protein and were expressed as ng./mg. (HA test) and mU/mg. (HAase test), respectively. Results: The urinary HA levels were elevated (2.5 to 6.5 fold) in bladder cancer patients (1173.7 ± 173.4; n = 261) as compared with normals (246.1 ± 38.5; n = 41); GU patients (306.6 ± 32.2; n = 133), and patients with a HxBCa (351.1 ± 49.1; n = 69) (p <0.001). The urinary HAase levels were elevated (3 to 7 fold) in G2/G3 bladder cancer patients (26.2 ± 3.2) as compared with normals (4.5 ± 0.9) and patients with either GU conditions (5.8 ± 1.3), HxBCa (8.2 ± 2.6) or G1 tumors (9.7 ± 2.5) (p <0.001). The HA test showed 83.1% sensitivity, 90.1% specificity and 86.5% accuracy in detecting bladder cancer, regardless of the tumor grade. The HAase test showed 81.5% sensitivity, 83.8% specificity and 82.9% accuracy to detect G2/G3 patients. Combining the inferences of the HA and HAase tests (HA-HAase test) resulted in detection of bladder cancer, regardless of tumor grade and stage, with higher sensitivity (91.2%) and accuracy (88.3%), and comparable specificity (84.4%). Conclusion: Our results show that the HA-HAase urine test is a noninvasive, highly sensitive and specific method for detecting bladder cancer and evaluating its grade. References 1 : Cancer Statistics, 1998. CA Cancer J Clin1998; 48: 6. 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Link, Google Scholar From the Departments of Urology, Cell Biology and Anatomy, and Epidemiology, University of Miami School of Medicine, Miami, Florida© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byBenitez A, Yates T, Shamaldevi N, Bowen T and Lokeshwar V (2018) Dietary Supplement Hymecromone and Sorafenib: A Novel Combination for the Control of Renal Cell CarcinomaJournal of Urology, VOL. 190, NO. 1, (285-290), Online publication date: 1-Jul-2013.Eissa S, Swellam M, Shehata H, El-Khouly I, El-Zayat T and El-Ahmady O (2018) Expression of HYAL1 and Survivin RNA as Diagnostic Molecular Markers for Bladder CancerJournal of Urology, VOL. 183, NO. 2, (493-498), Online publication date: 1-Feb-2010.Gomez C, Gomez P, Knapp J, Jorda M, Soloway M and Lokeshwar V (2018) Hyaluronic Acid and HYAL-1 in Prostate Biopsy Specimens: Predictors of Biochemical RecurrenceJournal of Urology, VOL. 182, NO. 4, (1350-1356), Online publication date: 1-Oct-2009.Lokeshwar V, Selzer M, Unwala D, Estrella V, Gomez M, Golshani R, Kester R, Klumpp D and Gousse A (2018) Uronate Peaks and Urinary Hyaluronic Acid Levels Correlate With Interstitial Cystitis SeverityJournal of Urology, VOL. 176, NO. 3, (1001-1007), Online publication date: 1-Sep-2006.MAROCLO M, PEREIRA S, SAMPAIO F and CARDOSO L (2018) URINARY GLYCOSAMINOGLYCAN EXCRETION DURING THE MENSTRUAL CYCLE IN NORMAL YOUNG WOMENJournal of Urology, VOL. 173, NO. 5, (1789-1792), Online publication date: 1-May-2005.SCHROEDER G, LORENZO-GOMEZ M, HAUTMANN S, FRIEDRICH M, EKICI S, HULAND H and LOKESHWAR V (2018) A SIDE BY SIDE COMPARISON OF CYTOLOGY AND BIOMARKERS FOR BLADDER CANCER DETECTIONJournal of Urology, VOL. 172, NO. 3, (1123-1126), Online publication date: 1-Sep-2004.RETZ M, LEHMANN J, AMANN E, WULLICH B, RÖDER C and STÖCKLE M (2018) Mucin 7 and Cytokeratin 20 as New Diagnostic Urinary Markers for Bladder TumorJournal of Urology, VOL. 169, NO. 1, (86-89), Online publication date: 1-Jan-2003.Lokeshwar V and Soloway M (2018) RE: URINE BASED MARKERS OF UROLOGICAL MALIGNANCYJournal of Urology, VOL. 167, NO. 3, (1406-1407), Online publication date: 1-Mar-2002.Konety B and Getzenberg R (2018) RE: URINE BASED MARKERS OF UROLOGICAL MALIGNANCYJournal of Urology, VOL. 167, NO. 3, (1407-1407), Online publication date: 1-Mar-2002.HAUTMANN S, LOKESHWAR V, SCHROEDER G, CIVANTOS F, DUNCAN R, GNANN R, FRIEDRICH M and SOLOWAY M (2018) ELEVATED TISSUE EXPRESSION OF HYALURONIC ACID AND HYALURONIDASE VALIDATES THE HA-HAase URINE TEST FOR BLADDER CANCERJournal of Urology, VOL. 165, NO. 6 Part 1, (2068-2074), Online publication date: 1-Jun-2001.LOKESHWAR V and SOLOWAY M (2018) CURRENT BLADDER TUMOR TESTS: DOES THEIR PROJECTED UTILITY FULFILL CLINICAL NECESSITY?Journal of Urology, VOL. 165, NO. 4, (1067-1077), Online publication date: 1-Apr-2001. Volume 163Issue 1January 2000Page: 348-356 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordshyaluronic acid (HA)metastasishyaluronidase (HAase)angiogenesisbladder cancer markerscancer detectionMetricsAuthor Information VINATA B. LOKESHWAR More articles by this author CAN ÖBEK More articles by this author HENRI T. PHAM More articles by this author DAVID WEI More articles by this author MARVIN J. YOUNG More articles by this author ROBERT C. DUNCAN More articles by this author MARK S. SOLOWAY More articles by this author NORMAN L. BLOCK More articles by this author Expand All Advertisement PDF downloadLoading ...