Characterization of Fibrillar Collagens and Extracellular Matrix of Glandular Benign Prostatic Hyperplasia Nodules

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.

Comparison of Picrosirius Red Staining With Second Harmonic Generation Imaging for the Quantification of Clinically Relevant Collagen Fiber Features in Histopathology Samples

“…36 PSR has already been exploited to understand collagen changes in cancer and other pathologies associated with fibrosis. 16,18,[37][38][39] Consistent with our previous observations, 12 stromal collagen appears more elongated and aligned in the immediate stroma surrounding malignant ducts compared with normal pancreas ducts when examined using PSR-POL (Fig. 2).…”

“…S2) 11 and prostate ( Supplementary Fig. S3) 38 cancers using PSR-POL. To validate the utility of PSR-POL to detect collagen changes, we acquired images around histologically confirmed normal and malignant pancreatic ducts.…”

Defective signaling, osteoblastogenesis, and bone remodeling in a mouse model of connexin43 C-terminal truncation

“…7B). This was confirmed by quantification of the birefringence hue distribution, with red indicating thicker more cross-linked fibers and green indicating thinner, less cross-linked fibers (Bauman et al, 2014;Whittaker and Rich, 2005 ); see Materials and Methods for the definitions of the parameters. Graphs depict mean±s.d.…”

“…Picrosirius Red staining was performed on sections, which were allowed to air dry before imaging. Quantification of fiber thickness and orientation was completed using a hue range method (Bauman et al, 2014;Whittaker and Rich, 2005). For dynamic parameters, 6-week-old mice of each genotype were injected with calcein (7.5 mg/kg body weight) and alizarin 3-methyl iminodiacetic acid (30 mg/kg body weight) at 7 and 2 days before euthanasia, respectively.…”

Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells

“…Paraffin-embedded, 5-μm sections of early lesions were stained with picrosirius red as previously described [40]. Polarized light microscopy with a × 10 objective was utilized to assess birefringence that is specific to fibrillar collagens.…”