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

Abstract

BackgroundFor 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. ObjectiveWe 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). MeasurementsHA 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 limitationsHA 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). ConclusionsHYAL-1 is a potential prognostic marker for predicting progression to muscle invasion and recurrence.