Abstract

BackgroundRefinement of parameters defining prostate cancer (PC) prognosis are urgently needed to identify patients with indolent versus aggressive disease. The Canadian Prostate Cancer Biomaker Network (CPCBN) consists of researchers from four Canadian provinces to create a validation cohort to address issues dealing with PC diagnosis and management.MethodsA total of 1512 radical prostatectomy (RP) specimens from five different biorepositories affiliated with teaching hospitals were selected to constitute the cohort. Tumoral and adjacent benign tissues were arrayed on tissue microarrays (TMAs). A patient clinical database was developed and includes data on diagnosis, treatment and clinical outcome.ResultsMean age at diagnosis of patients in the cohort was 61 years. Of these patients, 31% had a low grade (≤6) Gleason score (GS), 55% had GS 7 (40% of 3 + 4 and 15% of 4 + 3) and 14% had high GS (≥8) PC. The median follow-up of the cohort was 113 months. A total of 34% had a biochemical relapse, 4% developed bone metastasis and 3% of patients died from PC while 9% died of other causes. Pathological review of the TMAs confirmed the presence of tumor and benign tissue cores for > 94% of patients. Immunohistochemistry and FISH analyses, performed on a small set of specimens, showed high quality results and no biorepository-specific bias.ConclusionsThe CPCBN RP cohort is representative of real world PC disease observed in the Canadian population. The frequency of biochemical relapse and bone metastasis as events allows for a precise assessment of the prognostic value of biomarkers. This resource is available, in a step-wise manner, for researchers who intend to validate prognostic biomarkers in PC. Combining multiple biomarkers with clinical and pathologic parameters that are predictive of outcome will aid in clinical decision-making for patients treated for PC.

Highlights

  • Refinement of parameters defining prostate cancer (PC) prognosis are urgently needed to identify patients with indolent versus aggressive disease

  • We report a Tissue microarray (TMA)-based validation process which includes assembly of a retrospective multi-center radical prostatectomy (RP) cohort to build TMAs that will evaluate both biomarkers and their utility in identifying patients at high risk for biochemical recurrence (BCR) and the development of metastases or PC-specific mortality

  • We report on the quality control of this RP TMA series with quality assessments and controls, focusing on the TMA suitability for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques

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Summary

Introduction

Refinement of parameters defining prostate cancer (PC) prognosis are urgently needed to identify patients with indolent versus aggressive disease. The inability to clearly distinguish indolent versus aggressive disease is a major challenge for physicians caring for patients with prostate cancer (PC) [1]. Patients are stratified into groups ranging from very low to very high risk based on prostate-specific antigen (PSA) levels at time of diagnosis, tumor Gleason score (GS) in biopsies, and tumor stage at clinical presentation [2,3,4]. Several emerging biomarker candidates have been described; none so far have been fully validated or robust enough to be added to clinical parameters used in practice. Current strategies aspire to multiplex approaches combining current clinical parameters with a comprehensive panel of biomarkers to improve diagnostic accuracy of disease status and resolve the heterogeneity that confounds risk stratification in PC [2]

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