Glandular Benign Prostatic Hyperplasia Research Articles

Amide Proton Transfer Could Provide More Accurate Lesion Characterization in the Transition Zone of the Prostate.

There is an overlap comparing transition zone prostate cancer (TZ PCa) and benign prostatic hyperplasia (BPH) on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), creating additional challenges for assessment of TZ tumors on MRI. To evaluate whether amide proton transfer-weighted (APTw) imaging provides new diagnostic ideas for TZ PCa. Prospective. A total of 51 TZ PCa patients (age, 49-89), 44 stromal BPH (age, 57-92), and 45 glandular BPH patients (age, 56-92). A 3 T; T2WI turbo spin echo (TSE), quantitative T2*-weighted imaging, DWI echo planar imaging, 3D APTw TSE. Differences in APTw, apparent diffusion coefficient (ADC), and T2* among three lesions were compared by one-way analysis of variance (ANOVA). Regions of interest were drawn by two radiologists (X.Q.Z. and X.Y.Q., with 21 and 15 years of experience, respectively). Multivariable logistic regression analyses; ANOVA with post hoc testing; receiver operator characteristic curve analysis; Delong test. Significance level: P < 0.05. APTw among TZ PCa, stromal BPH, and glandular BPH (3.48% ± 0.83% vs. 2.76% ± 0.49% vs. 2.72% ± 0.45%, respectively) were significantly different except between stromal BPH and glandular BPH (P >0.99). Significant differences were found in ADC (TZ PCa 0.76 ± 0.16 × 10-3 mm2 /sec vs. stromal BPH 0.91 ± 0.14 × 10-3 mm2 /sec vs. glandular BPH 1.08 ± 0.18 × 10-3 mm2 /sec) among three lesions. APTw (OR=12.18, 11.80, respectively) and 1/ADC (OR=703.87, 181.11, respectively) were independent predictors of TZ PCa from BPH and stromal BPH. The combination of APTw and ADC had better diagnostic performance in the identification of TZ PCa from BPH and stromal BPH. APTw imaging has the potential to be of added value to ADC in differentiating TZ PCa from BPH and stromal BPH. 2 TECHNICAL EFFICACY: Stage 2.

Tight junction protein claudin-1 is downregulated by TGF-β1 via MEK signaling in benign prostatic epithelial cells.

Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF-β1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin-1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin-1 in the prostatic epithelial barrier and its regulation by TGF-β1 in prostatic epithelial cells are not clear. The expression of claudin-1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH-1 and BHPrE1 were treated with TGF-β1 and transfected with small interfering RNAs specific to claudin-1. Epithelial monolayer permeability changes in the treated cells were measured using trans-epithelial electrical resistance (TEER). The expression of claudin-1, E-cadherin, N-cadherin, snail, slug, and activation of mitogen-activated proteins kinases (MAPKs) and AKT was assessed following TGF-β1 treatment using Western blot analysis. Claudin-1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF-β1 treatment or claudin-1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF-β1 decreased levels of claudin-1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal-regulated kinase-1/2 (ERK-1/2) in both BPH-1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin-1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK-1/2 (ie, MEK-1/2) restored claudin-1 expression level as well as the epithelial barrier. Our findings suggest that downregulation of claudin-1 by TGF-β1 acting through the noncanonical MEK-1/2/ERK-1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF-β1 may contribute to claudin-1 downregulation and compromised epithelial barrier in clinical BPH specimens.

Revisiting quantitative multi-parametric MRI of benign prostatic hyperplasia and its differentiation from transition zone cancer.

This study investigates the multiparametric MRI (mpMRI) appearance of different types of benign prostatic hyperplasia (BPH) and whether quantitative mpMRI is effective in differentiating between prostate cancer (PCa) and BPH. Patients (n = 60) with confirmed PCa underwent preoperative 3T MRI. T2-weighted, multi-echo T2-weighted, diffusion weighted and dynamic contrast enhanced images (DCE) were obtained prior to undergoing prostatectomy. PCa and BPH (cystic, glandular or stromal) were identified in the transition zone and matched with MRI. Quantitative mpMRI metrics: T2, ADC and DCE-MRI parameters using an empirical mathematical model were measured. ADC values were significantly lower (p < 0.001) in PCa compared to all BPH types and can differentiate between PCa and BPH with high accuracy (AUC = 0.87, p < 0.001). T2 values were significantly lower (p < 0.001) in PCa compared to cystic BPH only, while glandular (p = 0.27) and stromal BPH (p = 0.99) showed no significant difference from PCa. BPH mimics PCa in the transition zone on DCE-MRI evidenced by no significant difference between them. mpMRI values of glandular (ADC = 1.31 ± 0.22µm2/ms, T2 = 115.7 ± 37.3ms) and cystic BPH (ADC = 1.92 ± 0.43µm2/ms, T2 = 242.8 ± 117.9ms) are significantly different. There was no significant difference in ADC (p = 0.72) and T2 (p = 0.46) between glandular and stromal BPH. Multiparametric MRI and specifically quantitative ADC values can be used for differentiating PCa and BPH, improving PCa diagnosis in the transition zone. However, DCE-MRI metrics are not effective in distinguishing PCa and BPH. Glandular BPH are not hyperintense on ADC and T2 as previously thought and have similar quantitative mpMRI measurements to stromal BPH. Glandular and cystic BPH appear differently on mpMRI and are histologically different.

PD25-10 CHARACTERIZATION OF FIBRILLAR COLLAGENS AND EXTRACELLULAR MATRIX OF GLANDULAR BENIGN PROSTATIC HYPERPLASIA NODULES

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Evaluation & Markers1 Apr 2014PD25-10 CHARACTERIZATION OF FIBRILLAR COLLAGENS AND EXTRACELLULAR MATRIX OF GLANDULAR BENIGN PROSTATIC HYPERPLASIA NODULES Tyler Bauman, Tristan Nicholson, Brett Becker, Wei Huang, and William Ricke Tyler BaumanTyler Bauman More articles by this author , Tristan NicholsonTristan Nicholson More articles by this author , Brett BeckerBrett Becker More articles by this author , Wei HuangWei Huang More articles by this author , and William RickeWilliam Ricke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1989AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies have associated prostatic fibrosis with lower urinary tract symptoms (LUTS) independent of hyperplasia, indicating that fibrosis may be important in evaluating benign prostatic hyperplasia (BPH). However, collagen and extracellular matrix (ECM) composition within the normal and hyperplastic prostate have not previously been characterized. The purpose of this study was to evaluate collagen and ECM in normal prostate tissue and in glandular BPH, as well as the effects of therapies on these parameters. METHODS Fibrillar collagen and ECM were assessed in prostate tissues stained for picrosirius red (PSR) and Masson’s trichrome (MTC), respectively, using a tissue microarray (TMA) with glandular BPH tissue from patients with LUTS and normal prostate tissue from prostatectomy specimens. Additional tissues from BPH patients who underwent transurethral resection of the prostate (TURP) were assessed from patients treated with 5α-reductase inhibitors (5α-RIs) (n = 22) ± α-blockers (n = 38). Images were acquired and tissues were quantified in ImageJ. RESULTS Total collagen staining, quantified by birefringence of PSR-stained tissues viewed under circularly polarized light, was similar in normal prostate tissue (n = 48) and glandular BPH (n = 23) (125.9 ± 4.9 vs. 111.9 ± 5.1; p = 0.08). Differences of collagen bundle size were also assessed and no differences were observed. No differences were observed in the quantity of ECM in normal and BPH tissue quantified with MTC (12.97 ± 1.03 vs. 10.20 ± 1.24; p = 0.11). Collagen staining intensity was not associated with age (p = 0.63). In tissues from TURP specimens, treatment with 5α-RIs (p = 0.71) or α-blockers (p = 0.69) had no effect on total collagen staining (n = 47). Collagen staining was not associated with age (p = 0.61), pre-TURP prostate-specific antigen (p = 0.87), pre-TURP AUA symptom index (p = 0.11), or pre-TURP post-void residual (p = 0.67). CONCLUSIONS The association between fibrosis and LUTS that has been demonstrated in previous studies cannot be explained by increased fibrillar collagen or extracellular matrix deposition in glandular BPH nodules. If fibrosis is associated with BPH/LUTS, it is likely affecting collagen and ECM deposition within the periurethral tissue independent of nodular BPH. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e729 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Tyler Bauman More articles by this author Tristan Nicholson More articles by this author Brett Becker More articles by this author Wei Huang More articles by this author William Ricke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Dynamic contrast-enhanced MRI and MR diffusion imaging to distinguish between glandular and stromal prostatic tissues.

To compare peak enhancement (PE), determined from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and the magnetic resonance (MR) directionally-averaged apparent diffusion coefficient (<D>) in glandular versus stromal prostatic tissues and, with this comparison, to infer if the hypothesis that gadolinium-DTPA (Gd-DTPA) does not enter healthy glands or ducts is plausible. MRI, MR spectroscopic imaging, DCE MRI and MR diffusion were evaluated in 17 untreated subjects with suspected or proven prostate cancer. PE and <D> were compared in glandular-ductal tissues [normal peripheral zone and glandular benign prostatic hyperplasia (BPH)] and stromal-low ductal tissues (central gland/mixed BPH and stromal BPH). The glandular-ductal tissues had lower PE [125+/-6.4 (% baseline)] and higher <D> [1.57+/-0.15 (s/10(-3) mm2)] than the stromal-low ductal tissues [PE=132+/-5.5 (% baseline) (P< .0008), <D>=1.18+/-0.20 (s/10(-3) mm2) (P< 1 x 10(-8))]. A statistical model based upon stepwise regression was generated and completely separated the tissue types: ductal Measure = 448+669 x<D> (s/10(-3) mm2)-10.7 x PE (1/%), R2=1.0 and P<8 x 10(-10). The very different MR results in the glandular-ductal versus stromal-low ductal tissues suggest that these tissues have different underlying structure. These results support the hypothesis that Gd-DTPA does not enter healthy prostatic glands or ducts. This may explain the higher PE and lower <D> that previously have been reported in prostate cancer versus healthy tissue.

Dynamic Contrast-Enhanced MRI in Normal and Abnormal Prostate Tissues as Defined by Biopsy, MRI, and 3D MRSI

This study characterized dynamic contrast-enhanced (DCE) MRI of prostate tissues: cancerous peripheral zone (PZ), normal PZ, stromal benign prostatic hyperplasia (BPH), and glandular BPH. MRI, MRSI, and DCE MRI were performed on 25 patients. Tissues were identified with MRI, MRSI, and (when available) biopsy results. Motion between MRI and DCE MRI, and within DCE MRI was assessed and manually corrected. To assess tissue and patient effects, native T1's were measured in 12 of 25 patients, and DCE MRI results were normalized to muscle enhancement. Regions of cancer had a higher peak enhancement (P < 0.006), faster enhancement rate (P < 0.0008), and faster washout slope (P < 0.05) than normal PZ tissues. Stromal BPH had the fastest enhancement rate (P < 0.003) of all tissues and tended to have the greatest enhancement. Intersequence motion averaged 2.6 mm and reached 7.9 mm. Motion within DCE MRI was generally minimal (<2 pixels), but one case showed a large shift that would have confounded the results. Native T1's were similar across the prostatic tissues. Interpatient variability in DCE MRI was only partially reduced by normalization to muscle. DCE MRI of the prostate discriminated PZ cancer from normal PZ tissues and predominantly stromal and glandular BPH. Magn Reson Med 53:249–255, 2005. © 2005 Wiley-Liss, Inc.

Dynamic contrast‐enhanced MRI in normal and abnormal prostate tissues as defined by biopsy, MRI, and 3D MRSI

This study characterized dynamic contrast-enhanced (DCE) MRI of prostate tissues: cancerous peripheral zone (PZ), normal PZ, stromal benign prostatic hyperplasia (BPH), and glandular BPH. MRI, MRSI, and DCE MRI were performed on 25 patients. Tissues were identified with MRI, MRSI, and (when available) biopsy results. Motion between MRI and DCE MRI, and within DCE MRI was assessed and manually corrected. To assess tissue and patient effects, native T1's were measured in 12 of 25 patients, and DCE MRI results were normalized to muscle enhancement. Regions of cancer had a higher peak enhancement (P < 0.006), faster enhancement rate (P < 0.0008), and faster washout slope (P < 0.05) than normal PZ tissues. Stromal BPH had the fastest enhancement rate (P < 0.003) of all tissues and tended to have the greatest enhancement. Intersequence motion averaged 2.6 mm and reached 7.9 mm. Motion within DCE MRI was generally minimal (<2 pixels), but one case showed a large shift that would have confounded the results. Native T1's were similar across the prostatic tissues. Interpatient variability in DCE MRI was only partially reduced by normalization to muscle. DCE MRI of the prostate discriminated PZ cancer from normal PZ tissues and predominantly stromal and glandular BPH.

Single-voxel oversampled J-resolved spectroscopy of in vivo human prostate tissue.

Single-voxel J-resolved spectroscopy with oversampling in the F1 dimension was used to obtain water unsuppressed 1H spectra of in situ human prostate tissue in 40 previously untreated prostate cancer patients. Based on T2-weighted MRI and previous biopsy information, voxels were placed in regions of benign or malignant peripheral zone tissue, or in regions of predominantly glandular or stromal benign prostatic hyperplasia (BPH) within the central gland. The addition of a second J-resolved dimension allowed for the observation of the J-modulation of citrate, as well as the resolution of polyamines from overlapping choline and creatine signals. Regions of healthy peripheral zone tissue and glandular BPH all demonstrated high levels of citrate and polyamines, with consistent coupling and J-modulation patterns. Conversely, regions of malignant peripheral zone tissue and stromal BPH demonstrated low levels of citrate and polyamines consistent with prior in vivo and ex vivo studies. Moreover, water T2 relaxation times determined for healthy peripheral zone tissue (mean 128 +/- 15.2 msec) were significantly different than for malignant peripheral zone tissue (mean 88.0 +/- 14.2 msec, P = 0.005), as well as for predominantly glandular (mean 92.4 +/- 12.2 msec, P = 0.009) and stromal BPH (mean 70.9 +/- 12.1 msec, P = 0.003). This preliminary study demonstrates that J-resolved spectroscopy of the in situ prostate can be acquired, and the information obtained from the second spectral dimension can provide additional physiologic information from human prostate tissue in a reasonable amount of time (< 10 min).

Prostatic carcinoma and benign prostatic hyperplasia: correlation of high-resolution MR and histopathologic findings.

High-resolution magnetic resonance (MR) imaging of 24 fresh radical prostatectomy specimens was performed on an experimental 1.9-T system. Direct correlation between the findings in 7-micron-thick macrosections and their corresponding MR images was possible. Fourteen patients had macroscopic evidence of cancer. In all 14 cases, the carcinoma nodules appeared as areas of low signal intensity on images obtained with a repetition time of 2,500 msec and an echo time of 80 msec. Ten of 14 nodules had well-defined margins and consisted of densely packed glandular elements, which displaced the surrounding normal glandular material of higher signal intensity. Ten specimens displayed benign prostatic hyperplasia (BPH). The MR characteristics of this entity were quite variable but relatively predictable, depending on the distribution and size of the glandular elements, as well as the composition of the surrounding stroma. In BPH, the changes began in the central portion of the gland. The areas of highest signal intensity corresponded to dilated glandular elements (cystic ectasia), while the areas of lowest signal intensity corresponded to collagen (scar) and fibromuscular stroma. Nodules of mixed glandular BPH and fibromuscular BPH were found to have signal intensities similar to those of well-differentiated nodules of prostatic adenocarcinoma.

Immunocytochemical Localization of Estrogen Receptors in Spontaneous and Experimentally Induced Canine Benign Prostatic Hyperplasia

Estrogens are believed to play a critical role in the etiology of canine benign prostatic hyperplasia (BPH); however, the mechanism has not been elucidated. To gain insight into this problem, we investigated the immunocytochemical localization of estrogen receptors (ER) in normal prostates, spontaneous BPH, and experimentally induced BPH by using a monoclonal ER antibody (H222). In all canine prostates the majority of ER was localized in nuclei of the same histological components: (1) transitional epithelium and subjacent stroma of the prostatic urethra, (2) periurethral prostatic ductal epithelium, and (3) prostatic stroma. ER content in the stroma was highest in the periurethral region of the prostate. Among the different groups of dogs, differences in ER location were seen only in the glandular epithelium. No ER was found in the glandular epithelium of normal prostates of young untreated dogs. In striking contrast, glandular epithelium of spontaneous BPH contained specific nuclear ER staining, though this staining was heterogeneous and was observed in only a minority (less than 10%) of the acinar epithelial cells. ER-positive acini in BPH were located predominantly in the periurethral region. These data demonstrate anatomical and biochemical heterogeneity of prostatic components and indicate that the estrogen sensitivity of prostatic cells is heterogeneous. If estrogen does play a role in BPH, it appears to act selectively rather than uniformly throughout the prostate. We reasoned that if glandular epithelial ER are involved in the development of spontaneous BPH, one might expect to find the same location of ER in BPH that was induced experimentally by specific types of treatment with androgens +/- estradiol. However, among hormone-treated dogs the presence of ER-positive prostatic glandular epithelium varied with the type of hormonal treatment but did not correlate with the experimental induction of glandular BPH. Some treatment groups with induced BPH had ER-positive prostatic glandular epithelial nuclei (with the same extent and pattern of ER localization as in spontaneous BPH); however, other treatment groups with induced BPH had ER-negative glandular epithelium. These data indicate either that glandular epithelial ER may not be involved in the pathogenesis of canine BPH or that there may be different types of BPH that have different etiologies. Possible mechanisms by which estrogen may affect the canine prostate are discussed in light of these new data on ER location.

Androgen receptor localization in the human prostate: Demonstration of heterogeneity using a new method of steroid receptor autoradiography

We have used a novel receptor labeling and autoradiographic technique to identify the cell types in human benign prostatic hyperplasia (BPH) that contain androgen receptors, and we have found that androgen receptor localization is heterogeneous. Prostatic androgen receptors were labeled by incubating slide-mounted frozen tissue sections (10 μm thickness) with [ 3H]R1881 in vitro. Tissue sections labeled in this way were subjected to concurrent biochemical and autoradiographic analysis. Some of the sections were wiped from the slides for scintillation counting to validate that the procedure indeed measures total cellular androgen receptors of appropriate high affinity and androgen steroid specificity. Replicate labeled slide-mounted tissue sections were dried rapidly, apposed to dry emulsion-coated coverslips, and exposed in the dark for autoradiography. Autoradiograms were developed, fixed, and stained; silver grains were counted over nuclei or cytoplasm of epithelium or strorna to evaluate specific androgen receptor location. Autoradiographic analysis of human glandular BPH demonstrated androgen receptor localization almost exclusively in the epithelial nuclei, with little or none in the stroma. We anticipate that data obtained using this new method of steroid receptor autoradiography may provide fresh insight into the mechanism of hormonal regulation of the prostate.

Immunocytochemical localization of estrogen receptors in spontaneous and experimentally induced canine benign prostatic hyperplasia

Estrogens are believed to play a critical role in the etiology of canine benign prostatic hyperplasia (BPH); however, the mechanism has not been elucidated. To gain insight into this problem, we investigated the immunocytochemical localization of estrogen receptors (ER) in normal prostates, spontaneous BPH, and experimentally induced BPH by using a monoclonal ER antibody (H222). In all canine prostates the majority of ER was localized in nuclei of the same histological components: (1) transitional epithelium and subjacent stroma of the prostatic urethra, (2) periurethral prostatic ductal epithelium, and (3) prostatic stroma. ER content in the stroma was highest in the periurethral region of the prostate. Among the different groups of dogs, differences in ER location were seen only in the glandular epithelium. No ER was found in the glandular epithelium of normal prostates of young untreated dogs. In striking contrast, glandular epithelium of spontaneous BPH contained specific nuclear ER staining, though this staining was heterogeneous and was observed in only a minority (less than 10%) of the acinar epithelial cells. ER-positive acini in BPH were located predominantly in the periurethral region. These data demonstrate anatomical and biochemical heterogeneity of prostatic components and indicate that the estrogen sensitivity of prostatic cells is heterogeneous. If estrogen does play a role in BPH, it appears to act selectively rather than uniformly throughout the prostate. We reasoned that if glandular epithelial ER are involved in the development of spontaneous BPH, one might expect to find the same location of ER in BPH that was induced experimentally by specific types of treatment with androgens +/- estradiol. However, among hormone-treated dogs the presence of ER-positive prostatic glandular epithelium varied with the type of hormonal treatment but did not correlate with the experimental induction of glandular BPH. Some treatment groups with induced BPH had ER-positive prostatic glandular epithelial nuclei (with the same extent and pattern of ER localization as in spontaneous BPH); however, other treatment groups with induced BPH had ER-negative glandular epithelium. These data indicate either that glandular epithelial ER may not be involved in the pathogenesis of canine BPH or that there may be different types of BPH that have different etiologies. Possible mechanisms by which estrogen may affect the canine prostate are discussed in light of these new data on ER location.

Testicular androgen and estrogen secretion and benign prostatic hyperplasia in the beagle.

The natural history of benign prostatic hyperplasia (BPH) in the dog is characterized by a slow progression through two phases. The early phase of the disease process is characterized by glandular hyperplasia and occurs as early as 2.5 yr of age. The late phase of the disease is characterized by cystic hyperplasia and occurs after 4 yr. The results of the present study are the first to compare Leydig cell structure and steroidogenic function in dogs with BPH with those in age-matched controls. It was discovered that glandular BPH can occur in young dogs (2.5 yr) in which Leydig cell mass and ultrastructure and maximally stimulated androgen secretion are indistinguishable from those in age-matched controls. These results support the concept that the early phase of BPH (glandular hyperplasia) is not related temporally to some defect in the Leydig cell. In contrast, the late phase of BPH (cystic hyperplasia) in beagles 6 yr of age is associated with diminished smooth endoplasmic reticulum in the Leydig cell and with diminished production of androgens by perfused testes in vitro. During the course of these studies, we discovered that the testes of young beagles with BPH, but not age-matched controls or old beagles with BPH, secrete an unidentified molecule (putative estrogen). This molecule was characterized partially in that it is extractable from testicular venous effluent with diethyl ether, elutes in a discrete fraction in several different high performance liquid chromatographic systems, reacts with an antibody that recognizes 17 beta-estradiol, estrone, and estriol, and competes with 17 beta-[3H]estradiol for the rat uterine estrogen receptor. Based on the elution volume from high performance liquid chromatography, the unknown molecule (putative estrogen) is not estriol, estradiol, or estrone.