title: Elevated levels of peritumoral chondroitin sulfate are predictive of poor prognosis in patients treated by radical prostatectomy for early-stage prostate cancer.
abstract: The disease course of localized prostate cancer is highly variable, and patients potentially curable by aggressive management are not readily identified by current clinical practice. Chondroitin sulfate (CS) glycosaminoglycan is a candidate biomarker as elevated levels of CS in peritumoral stroma of prostate cancer have been associated with prostate-specific antigen (PSA) failure. Immunoreactive CS was measured using image analysis of archived radical prostatectomy tissues, obtained from 157 men with a median of 47 months (range, 16-111 months) clinical follow-up. CS level, Gleason score, and preoperative serum PSA levels were independent predictors of PSA failure by Cox's multivariate analysis. Patients with low CS levels had significantly fewer PSA failures after radical prostatectomy than patients with high levels of CS (Kaplan-Meier plot; 32% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 50% for CS > or = 7.0, P = 0.0001). In the subgroup of patients with preoperative serum PSA levels < 10 ng/ml, CS was particularly useful in discriminating retrospectively those patients most suited for surgery (Kaplan-Meier plot; 14% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 47% for CS > or = 7.0, P = 0.0001). We conclude that measurements of CS level can assist in predicting patient outcome after surgery. Additionally, our data suggest that the combination of CS and PSA measurements may improve outcome prediction for patients with intermediate Gleason scores.
authors.affiliation: Oncology Unit, Flinders Cancer Centre, Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Ricciardelli
authors.forename: D I
authors.initials: DI
authors.lastname: Quinn
authors.forename: W A
authors.initials: WA
authors.lastname: Raymond
authors.forename: K
authors.initials: K
authors.lastname: McCaul
authors.forename: P D
authors.initials: PD
authors.lastname: Sutherland
authors.forename: P D
authors.initials: PD
authors.lastname: Stricker
authors.forename: J J
authors.initials: JJ
authors.lastname: Grygiel
authors.forename: R L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: V R
authors.initials: VR
authors.lastname: Marshall
authors.forename: W D
authors.initials: WD
authors.lastname: Tilley
authors.forename: D J
authors.initials: DJ
authors.lastname: Horsfall
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002809:Chondroitin Sulfates / Q000032:analysis*; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D002809:Chondroitin Sulfates; D017430:Prostate-Specific Antigen