Hyaluronic Acid and HYAL-1 in Prostate Biopsy Specimens: Predictors of Biochemical Recurrence

Abstract

Molecular markers could aid prostate specific antigen, biopsy Gleason sum and clinical stage to provide accurate information on prostate cancer progression. HYAL-1 hyaluronidase and hyaluronic acid staining in prostatectomy specimens predicts biochemical recurrence. We examined whether hyaluronic acid and HYAL-1 staining in biopsy specimens predicts biochemical recurrence and correlates with staining in matched prostatectomy specimens. Biopsy and prostatectomy specimens were obtained from 61 patients with clinically localized prostate cancer from multiple centers, including 23 with (group 1) and 38 without (group 2) biochemical recurrence. Mean followup was 103.1 months. Biotinylated hyaluronic acid binding protein and anti-HYAL-1 antibody were used for hyaluronic acid and HYAL-1 staining, respectively. Staining was graded between 0 and 300 depending on staining intensity and area. HYAL-1 and hyaluronic acid were expressed in tumor cells and stroma, respectively. In biopsy specimens HYAL-1 and hyaluronic acid expression was higher in group 1 than in group 2 (203.9 and 182.1 vs 48.8 and 87.0, respectively, p <0.0001). On univariate analysis hyaluronic acid, HYAL-1, biopsy Gleason and prostate specific antigen significantly predicted biochemical recurrence (p <0.001). On multivariate analysis only HYAL-1 staining independently predicted recurrence with an accuracy of 81.8% (p <0.001). In prostatectomy specimens only HYAL-1 staining correlated with staining in biopsy specimens (Spearman rho = 0.72, p = 0.0002) and predicted biochemical recurrence. To our knowledge this is the first report that HYAL-1 staining in biopsy specimens is an independent predictor of biochemical recurrence. This may be useful when selecting treatment.