Characterization of fibrillar collagens and extracellular matrix of glandular benign prostatic hyperplasia nodules.

Tyler M Bauman,William A Ricke,Tristan M Nicholson,Chad M Vezina,Wei Huang,Lisa L Abler,Kevin W Eliceiri,Michael R Emmert-Buck

doi:10.1371/journal.pone.0109102

Tyler M Bauman, William A Ricke + Show 6 more

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https://doi.org/10.1371/journal.pone.0109102

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Abstract

ObjectiveRecent studies have associated lower urinary tract symptoms (LUTS) in men with prostatic fibrosis, but a definitive link between collagen deposition and LUTS has yet to be demonstrated. The objective of this study was to evaluate ECM and collagen content within normal glandular prostate tissue and glandular BPH, and to evaluate the association of clinical parameters of LUTS with collagen content.MethodsFibrillar collagen and ECM content was assessed in normal prostate (48 patients) and glandular BPH nodules (24 patients) using Masson's trichrome stain and Picrosirius red stain. Second harmonic generation (SHG) imaging was used to evaluate collagen content. Additional BPH tissues (n = 47) were stained with Picrosirius red and the association between clinical parameters of BPH/LUTS and collagen content was assessed.ResultsECM was similar in normal prostate and BPH (p = 0.44). Total collagen content between normal prostate and glandular BPH was similar (p = 0.27), but a significant increase in thicker collagen bundles was observed in BPH (p = 0.045). Using SHG imaging, collagen content in BPH (mean intensity = 62.52; SEM = 2.74) was significantly higher than in normal prostate (51.77±3.49; p = 0.02). Total collagen content was not associated with treatment with finasteride (p = 0.47) or α-blockers (p = 0.52), pre-TURP AUA symptom index (p = 0.90), prostate-specific antigen (p = 0.86), post-void residual (PVR; p = 0.32), prostate size (p = 0.21), or post-TURP PVR (p = 0.51). Collagen content was not associated with patient age in patients with BPH, however as men aged normal prostatic tissue had a decreased proportion of thick collagen bundles.ConclusionsThe proportion of larger bundles of collagen, but not total collagen, is increased in BPH nodules, suggesting that these large fibers may play a role in BPH/LUTS. Total collagen content is independent of clinical parameters of BPH and LUTS. If fibrosis and overall ECM deposition are associated with BPH/LUTS, this relationship likely exists in regions of the prostate other than glandular hyperplasia.

Highlights

Lower urinary tract symptoms (LUTS) are a major medical problem with an estimated prevalence of 20% in men over 20 [1] and 70% in men over 80 [2]
Blue intensity was not significantly different between normal prostate tissue and glandular benign prostatic hyperplasia (BPH) (5.49660.940; p = 0.44; Figure 1), indicating that extracellular matrix (ECM) content is similar in normal prostate tissues and BPH
We investigated the association of collagen content with different clinical parameters of BPH and LUTS by staining an additional set of TURP specimens from 47 patients with Picrosirius red

Summary

Introduction

Lower urinary tract symptoms (LUTS) are a major medical problem with an estimated prevalence of 20% in men over 20 [1] and 70% in men over 80 [2]. A typical treatment regimen for symptomatic BPH includes aadrenergic antagonists (a-blockers) to relax smooth muscle and 5areductase inhibitors (5a-RIs) such as finasteride or dutasteride to block the conversion of testosterone to the more potent androgen dihydrotestosterone [4]. Many patients undergo surgical intervention if symptoms persist. While there are multiple non-prostatic explanations for LUTS [5], one proposed reason for treatment failure with a-blockers or 5a-RIs is collagen deposition within regions of the prostate as a result of fibrosis [6,7]

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