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.
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: James D Brooks; Wei Wei; Jonathan R Pollack; Robert B West; Jun Ho Shin; John B Sunwoo; Sarah J Hawley; Heidi Auman; Lisa F Newcomb; Jeff Simko; Antonio Hurtado-Coll; Dean A Troyer; Peter R Carroll; Martin E Gleave; Daniel W Lin; Peter S Nelson; Ian M Thompson; Lawrence D True; Jesse K McKenney; Ziding Feng; Ladan Fazli Journal: Prostate Date: 2016-06-21 Impact factor: 4.104
Authors: Alison Y Zhang; Karen Chiam; Ygal Haupt; Stephen Fox; Simone Birch; Wayne Tilley; Lisa M Butler; Karen Knudsen; Clay Comstock; Krishan Rasiah; Judith Grogan; Kate L Mahon; Tina Bianco-Miotto; Carmela Ricciardelli; Maret Böhm; Susan Henshall; Warick Delprado; Phillip Stricker; Lisa G Horvath; James G Kench Journal: Int J Cancer Date: 2018-12-04 Impact factor: 7.396
Authors: S R Lambert; N Mladkova; A Gulati; R Hamoudi; K Purdie; R Cerio; I Leigh; C Proby; C A Harwood Journal: Br J Cancer Date: 2013-12-12 Impact factor: 7.640
Authors: Marina Rigau; Mireia Olivan; Marta Garcia; Tamara Sequeiros; Melania Montes; Eva Colás; Marta Llauradó; Jacques Planas; Inés de Torres; Juan Morote; Colin Cooper; Jaume Reventós; Jeremy Clark; Andreas Doll Journal: Int J Mol Sci Date: 2013-06-17 Impact factor: 5.923
Authors: Tamara Sequeiros; Marta García; Melania Montes; Mireia Oliván; Marina Rigau; Eva Colás; Inés de Torres; Juan Morote; Jaume Reventós; Andreas Doll Journal: Biomed Res Int Date: 2013-11-25 Impact factor: 3.411