Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44V6 and microvessel density for prostate cancer

Sinan Ekici, Wolfgang H. Cerwinka, Robert Duncan, Pablo Gomez, Francisco Civantos, Mark S. Soloway, Vinata B Lokeshwar

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL-1 (hazard ratio = 8.196, p = 0.0009)/HA-HYAL-1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72-to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalInternational Journal of Cancer
Volume112
Issue number1
DOIs
StatePublished - Oct 20 2004

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Hyaluronoglucosaminidase
Hyaluronic Acid
Microvessels
Prostatic Neoplasms
Staining and Labeling
Recurrence
CD44 Antigens
Neoplasm Metastasis
Neoplasms
Nomograms
Neoplasm Grading
Seminal Vesicles
Cell Surface Receptors
Prostatectomy
Glycosaminoglycans
Tumor Burden
Proportional Hazards Models

Keywords

  • CD44v6
  • HYAL-1
  • Hyaluronic acid
  • Hyaluronidase
  • Microvessel density
  • Prognostic indicator
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44V6 and microvessel density for prostate cancer. / Ekici, Sinan; Cerwinka, Wolfgang H.; Duncan, Robert; Gomez, Pablo; Civantos, Francisco; Soloway, Mark S.; Lokeshwar, Vinata B.

In: International Journal of Cancer, Vol. 112, No. 1, 20.10.2004, p. 121-129.

Research output: Contribution to journalArticle

Ekici, Sinan ; Cerwinka, Wolfgang H. ; Duncan, Robert ; Gomez, Pablo ; Civantos, Francisco ; Soloway, Mark S. ; Lokeshwar, Vinata B. / Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44V6 and microvessel density for prostate cancer. In: International Journal of Cancer. 2004 ; Vol. 112, No. 1. pp. 121-129.
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abstract = "Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96{\%}, 84{\%}, 84{\%}, 68{\%} and 76{\%} sensitivity, respectively. Specificity was, 61{\%} (HA), 80.5{\%} (HYAL-1), 87.8{\%} (HA-HYAL-1), 56.1{\%} (CD44v6) and 61{\%} (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL-1 (hazard ratio = 8.196, p = 0.0009)/HA-HYAL-1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72-to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.",
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T1 - Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44V6 and microvessel density for prostate cancer

AU - Ekici, Sinan

AU - Cerwinka, Wolfgang H.

AU - Duncan, Robert

AU - Gomez, Pablo

AU - Civantos, Francisco

AU - Soloway, Mark S.

AU - Lokeshwar, Vinata B

PY - 2004/10/20

Y1 - 2004/10/20

N2 - Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL-1 (hazard ratio = 8.196, p = 0.0009)/HA-HYAL-1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72-to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

AB - Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL-1 (hazard ratio = 8.196, p = 0.0009)/HA-HYAL-1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72-to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

KW - CD44v6

KW - HYAL-1

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KW - Hyaluronidase

KW - Microvessel density

KW - Prognostic indicator

KW - Prostate cancer

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