title: Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy.
abstract: The risk of metastatic progression for prostate cancer patients who undergo radical prostatectomy is best estimated presently based on prostate-specific antigen (PSA) doubling time (PSADT). However, additional markers of risk are needed to identify patients who may benefit from aggressive salvage treatment. A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy. We assessed the reliability with which AZPG1 expression could predict clinical recurrence and metastatic progression. Using immunohistochemical methods, we analyzed AZPG1 expression in malignant prostate epithelium in prostatectomy specimens from 228 prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was associated with clinical recurrence (defined as confirmed localized recurrence, metastasis, or death from prostate cancer; hazard ratio [HR] = 4.8, 95% confidence interval [CI] = 2.2 to 10.7, P<.001) and with bony metastases or death from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P<.001). Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these preliminary findings are validated in independent cohorts, the measurement of AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely assessment of risk of metastatic progression after radical prostatectomy.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia. s.henshall@garvan.org.au
authors.forename: Susan M
authors.initials: SM
authors.lastname: Henshall
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Eggleton
authors.forename: John J
authors.initials: JJ
authors.lastname: Grygiel
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stricker
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D012313:RNA / Q000378:metabolism; D012107:Research Design; D018570:Risk Assessment; D029589:Seminal Plasma Proteins / Q000235:genetics / Q000378:metabolism*; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D014408:Biomarkers, Tumor; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; D012313:RNA; D017430:Prostate-Specific Antigen