title: Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer.
abstract: BACKGROUND
  Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40-50% biochemical relapse rate at 5 years. Adjuvant radiotherapy improves biochemical progression-free and overall survival in men with positive margins, but is associated with increased toxicity. There is an urgent need to identify new prognostic markers to define the group of patients who would benefit from multimodality therapy.
  
  
  METHODS
  Nuclear β-catenin, membranous secreted frizzled-related protein 4 (sFRP4), zinc-alpha 2-glycoprotein (AZGP1), and macrophage inhibitory cytokine-1 (MIC-1) have previously been identified as molecular markers of outcome in localized PC. From these published studies, we identified a subset of patients with positive margins. The aim of this study was to assess the association between these four molecular markers and outcome in men with margin-positive, localized PC.
  
  
  RESULTS
  We identified 186 men with positive margins from 330 men with localized PC; 53% had preoperative PSA >10 ng/ml, 72% extraprostatic extension (EPE), 24% seminal vesicles involvement (SVI), and 57% RP Gleason score ≥ 7. AZGP1 (P = 0.009), membranous sFRP4 (P = 0.03) and MIC-1 (P = 0.04) expression predicted for biochemical relapse on univariate analysis. Only absent/low AZGP1 expression (P = 0.01) was an independent predictor of recurrence in margin-positive, localized PC when modeled with preoperative PSA (P = 0.2), EPE (P = 0.2), SVI (P = 0.4), Gleason score ≥ 7 (P = 0.5) and adjuvant treatment (P = 0.4). Furthermore, there was an association between absent/low AZGP1 expression and clinical recurrence (P = 0.007).
  
  
  CONCLUSIONS
  AZGP1 is a potential molecular marker for biochemical relapse in men with margin-positive, localized PC. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post-RP radiotherapy.
authors: Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors: Po Yee
authors: PY
authors: Yip
authors: James G
authors: JG
authors: Kench
authors: Krishan K
authors: KK
authors: Rasiah
authors: Ruth Pe
authors: RP
authors: Benito
authors: C-Soon
authors: CS
authors: Lee
authors: Phillip D
authors: PD
authors: Stricker
authors: Susan M
authors: SM
authors: Henshall
authors: Robert L
authors: RL
authors: Sutherland
authors: Lisa G
authors: LG
authors: Horvath
mesh_terms: D054392:Adipokines; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D015331:Cohort Studies; D018572:Disease-Free Survival; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D055436:Growth Differentiation Factor 15 / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis; D000090203:Zn-Alpha-2-Glycoprotein; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D055436:Growth Differentiation Factor 15; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C526140:GDF15 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins