HYAL-1 Hyaluronidase: A Potential Prognostic Indicator for Progression to Muscle Invasion and Recurrence in Bladder Cancer

Mario W. Kramer, Roozbeh Golshani, Axel S. Merseburger, Judith Knapp, Alfredo Garcia, Joerg Hennenlotter, Robert C. Duncan, Mark S. Soloway, Merce Jorda, Marcus A. Kuczyk, Arnulf Stenzl, Vinata B. Lokeshwar*

*Corresponding author for this work
51 Citations (Scopus)


Background: For bladder cancer (BCa) patients undergoing bladder-sparing treatments, molecular markers may aid in accurately predicting progression to muscle invasion and recurrence. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronoglucosaminidase 1 (HYAL-1)-type hyaluronidase (HAase) promotes tumor growth, invasion, and angiogenesis. Urinary HA and HAase levels are diagnostic markers for BCa. Objective: We evaluated whether HA and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non-muscle-invasive BCa. Design, setting, and participants: : Based on tissue availability, tissue microarrays were prepared from a cohort of 178 BCa specimens (144 non-muscle invasive, 34 muscle invasive). Follow-up information was available on 111 patients with non-muscle-invasive BCa (mean follow-up: 69.5 mo); 58 patients recurred and 25 progressed to muscle invasion (mean time to progress: 22.3 mo). Measurements: HA and HYAL-1 expression was evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with BCa recurrence and muscle invasion was evaluated by univariate and multivariate models. Results and limitations: HA and HYAL-1 expression correlated with tumor grade, stage, and multifocality (p < 0.05). In non-muscle-invasive BCa specimens, HYAL-1 staining was higher (234.3 ± 52.2; 200.6 ± 61.4) if patients experienced progression to muscle invasion or recurrence when compared with no progression or recurrence (164.1 ± 48.2; 172.1 ± 57; p < 0.001). HA staining correlated with muscle invasion (p < 0.001). In univariate analysis, age (p = 0.014), multifocality (p = 0.023), and HYAL-1 staining (p < 0.001) correlated with muscle invasion, whereas only HYAL-1 correlated with recurrence (p = 0.013). In multivariate analysis, HYAL-1 significantly associated with muscle invasion (p < 0.001; 76.8% accuracy) and recurrence (p = 0.01; 67.8% accuracy). Conclusions: HYAL-1 is a potential prognostic marker for predicting progression to muscle invasion and recurrence.

Original languageEnglish
JournalEuropean Urology
Issue number1
Pages (from-to)86-94
Number of pages9
Publication statusPublished - 01.2010

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


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