title: Arylsulfatase B (N-acetylgalactosamine-4-sulfatase): potential role as a biomarker in prostate cancer.
abstract: BACKGROUND
  The enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) degrades chondroitin-4-sulfate (C4S) and is reduced in malignant colonic and mammary tissues but has not previously been evaluated in prostate cancer.
  
  
  METHODS
  ARSB immunostaining was performed on two tissue microarrays (TMAs) and analyzed by digital image analysis, generating ARSB H-scores for prevalence and intensity of epithelial, stromal and combined epithelial and stromal immunostaining. Also, paired malignant and normal prostate tissues were analyzed for ARSB activity, C4S, total sulfated glycosaminoglycans and versican content. The quantities of C4S and of the epidermal growth factor receptor (EGFR) that co-immunoprecipitated with versican were determined in the normal and malignant paired prostate tissues.
  
  
  RESULTS
  Forty-four cases of prostate cancer were paired by age (± 5 years), race, Gleason score (in order) and pathological TNM (tumor, node, metastasis) score. The pairs differed by recurrence vs non-recurrence of elevated PSA at ≥ 4 years. When TMA cores were analyzed for ARSB H-score, 18 of the 22 pairs had lower ARSB H-scores in the recurrent member of the pair, whereas higher initial PSA values were associated with recurrence in only 65% of the paired cases. In a second TMA, Gleason scores 6 and 7 were associated with higher ARSB H-scores than Gleason scores 8 and 9 for stroma, epithelium and stroma and epithelium combined (P=0.052, P=0.015, P<0.0001, respectively) and were inversely correlated (r=-0.98, -0.97 and -0.99, respectively). In other paired normal and malignant prostate tissues, ARSB activity was significantly higher in the normal tissues, and C4S and versican values were lower (P<0.0001). C4S that co-immunoprecipitated with versican was greater in the malignant than in the normal tissue, whereas total EGFR that co-immunoprecipitated with versican was reduced.
  
  
  CONCLUSIONS
  Study findings suggest that ARSB may be useful as a prognostic biomarker in prostate cancer and that the biological action of ARSB on chondroitin sulfate may impact upon versican's effects in the tumor microenvironment.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: L
authors.initials: L
authors.lastname: Feferman
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: R
authors.initials: R
authors.lastname: Deaton
authors.forename: P
authors.initials: P
authors.lastname: Gann
authors.forename: G
authors.initials: G
authors.lastname: Guzman
authors.forename: A
authors.initials: A
authors.lastname: Kajdacsy-Balla
authors.forename: J K
authors.initials: JK
authors.lastname: Tobacman
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006025:Glycosaminoglycans; C512478:EGFR protein, human; D066246:ErbB Receptors; D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human