Urinary 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, Norman L Block

Research output: Contribution to journalArticle

153 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)348-356
Number of pages9
JournalJournal of Urology
Volume163
Issue number1
StatePublished - Jan 1 2000

Fingerprint

Hyaluronoglucosaminidase
Hyaluronic Acid
Urinary Bladder Neoplasms
Neoplasms
Urine
CD44 Antigens
Sensitivity and Specificity
Transitional Cell Carcinoma
Glycoside Hydrolases
Glycosaminoglycans
Routine Diagnostic Tests
Enzyme-Linked Immunosorbent Assay
Quality of Life
Neoplasm Metastasis
Carcinoma

Keywords

  • Angiogenesis
  • Bladder cancer markers
  • Cancer detection
  • Hyaluronic acid (HA)
  • Hyaluronidase (HAase)
  • Metastasis

ASJC Scopus subject areas

  • Urology

Cite this

Lokeshwar, V. B., Öbek, C., Pham, H. T., Wei, D., Young, M. J., Duncan, R. C., ... Block, N. L. (2000). Urinary hyaluronic acid and hyaluronidase: Markers for bladder cancer detection and evaluation of grade. Journal of Urology, 163(1), 348-356.

Urinary hyaluronic acid and hyaluronidase : Markers for bladder cancer detection and evaluation of grade. / Lokeshwar, Vinata B.; Öbek, Can; Pham, Henri T.; Wei, David; Young, Marvin J.; Duncan, Robert C.; Soloway, Mark S.; Block, Norman L.

In: Journal of Urology, Vol. 163, No. 1, 01.01.2000, p. 348-356.

Research output: Contribution to journalArticle

Lokeshwar, VB, Öbek, C, Pham, HT, Wei, D, Young, MJ, Duncan, RC, Soloway, MS & Block, NL 2000, 'Urinary hyaluronic acid and hyaluronidase: Markers for bladder cancer detection and evaluation of grade', Journal of Urology, vol. 163, no. 1, pp. 348-356.
Lokeshwar VB, Öbek C, Pham HT, Wei D, Young MJ, Duncan RC et al. Urinary hyaluronic acid and hyaluronidase: Markers for bladder cancer detection and evaluation of grade. Journal of Urology. 2000 Jan 1;163(1):348-356.
Lokeshwar, Vinata B. ; Öbek, Can ; Pham, Henri T. ; Wei, David ; Young, Marvin J. ; Duncan, Robert C. ; Soloway, Mark S. ; Block, Norman L. / Urinary hyaluronic acid and hyaluronidase : Markers for bladder cancer detection and evaluation of grade. In: Journal of Urology. 2000 ; Vol. 163, No. 1. pp. 348-356.
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T1 - Urinary hyaluronic acid and hyaluronidase

T2 - Markers for bladder cancer detection and evaluation of grade

AU - Lokeshwar, Vinata B.

AU - Öbek, Can

AU - Pham, Henri T.

AU - Wei, David

AU - Young, Marvin J.

AU - Duncan, Robert C.

AU - Soloway, Mark S.

AU - Block, Norman L

PY - 2000/1/1

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N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Bladder cancer markers

KW - Cancer detection

KW - Hyaluronic acid (HA)

KW - Hyaluronidase (HAase)

KW - Metastasis

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