A Comprehensive Approach Toward Novel Serum Biomarkers for Benign Prostatic Hyperplasia: The MPSA Consortium

Purpose

Clinical benign prostatic hyperplasia is primarily diagnosed based on a diverse array of progressive lower urinary tract symptoms and is likely distinct from histological benign prostatic hyperplasia, which is detected by the presence of nonmalignant proliferation of prostate cells but may or may not be associated with symptoms. Pharmacological management of lower urinary tract symptoms has emerged as an effective initial treatment for clinical benign prostatic hyperplasia due to the introduction of new drug therapies shown to be effective in recent large clinical trials. Despite advances in symptom management and research into disease pathology, diagnostic strategies for the prediction of benign prostatic hyperplasia progression and response to drug modalities are lacking, and questions remain as to the molecular differences underlying clinical (symptomatic) vs histological (nonsymptomatic) benign prostatic hyperplasia.

Materials and Methods

As part of the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, which demonstrated the effectiveness of combination drug therapy in slowing benign prostatic hyperplasia progression, an archive of biological specimens linked to clinical data was collected for future profiling of disease pathology and changes associated with response to drug therapy. The MTOPS Prostatic Samples Analysis (MPSA) Consortium was established to identify and validate molecular markers that may better define benign prostatic hyperplasia related pathologies, identify risk of progression of lower urinary tract symptoms, and predict response to drug therapy using the MTOPS archive. The cooperating MPSA Biomarker Discovery Sites and Pathology Coordinating Center use diverse methodologies and scientific approaches as well as unique expertise to address the goals of the Consortium.

Results

To date the MPSA has identified a number of promising biomarkers as well as other molecular and cellular changes associated with benign prostatic hyperplasia.

Conclusions

These findings and ongoing Consortium discovery efforts have the potential to provide a greater understanding of the defects underlying disease pathology, and may lead to the development of early and more effective pharmacological treatment strategies for benign prostatic hyperplasia.

Key Words: prostatic hyperplasia, urologic diseases, biological markers

Abbreviations and Acronyms: α2-M, α2 macroglobulin, AREG, amphiregulin, AUA, American Urological Association, BPH, benign prostatic hyperplasia, BPH-A, BPH antigen, CGA, chromogranin A, EAC, external advisory committee, ELISA, enzyme linked immunosorbant assay, fPSA, free prostate specific antigen, IL-6, interleukin 6, LCM, laser capture microscopy, LUTS, lower urinary tract symptoms, MMP1, matrix metalloproteinase 1, MPSA, MTOPS Prostatic Samples Analysis, MTOPS, Medical Therapy of Prostatic Symptoms, NIA, National Institute on Aging, NIDDK, National Institute of Diabetes and Digestive and Kidney Disease, NIH, National Institutes of Health, PCC, Pathology Coordinating Center, PSA, prostate specific antigen, PSTN, periostin, Qmax, maximum urinary flow rate, qRT-PCR, quantitative reverse transcription polymerase chain reaction, T0, time zero, TZ, transition zone, VITN, vitronectin