TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA) using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancer tissues using a combined immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial neoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role). Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5%) of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combined pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. In conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Given the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtyping prostate cancer based on ERG rearrangement status and suggests clinical utility in prostate needle biopsy evaluation.
Purpose To compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men. Experimental design Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared to 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing. Results ERG rearrangement was identified in 48/113 tumors (42.5%) in CaM and 29/105 tumors (27.6%) in AAM (p=0.024). PTEN deletion was seen in 19/96 tumors (19.8%) in CaM and 7/101 tumors (6.9%) in AAM (p=0.011). SPINK1 overexpression was present in 9/110 tumors (8.2%) in CaM and 25/105 tumors (23.4%) in AAM (p=0.002). SPOP mutation was identified in 8/78 (10.3%) tumors in CaM and 4/88 (4.5%) tumors in AAM (p=0.230). When adjusted for age, BMI, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (p=0.018 and p=0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (p=0.061 and p=0.087, respectively). Conclusions Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, while ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine if these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups.
Cystitis, or inflammation of the bladder, has a direct effect on bladder function. Interstitial cystitis is a syndrome characterized by urinary bladder pain and irritative symptoms of more than 6 months duration. It commonly occurs in young to middle-aged women with no known cause and in fact represents a diagnosis of exclusion. Many factors have been suggested, including chronic or subclinical infection, autoimmunity and genetic susceptibility, which could be responsible for initiating the inflammatory response. However, a central role of inflammation has been confirmed in the pathogenesis of interstitial cystitis. Patients with interstitial cystitis are usually managed with multimodal therapy to break the vicious cycle of chronic inflammation at every step. Patients who develop irreversible pathologies such as fibrosis are managed surgically, which is usually reserved for refractory cases.
What ' s known on the subject? and What does the study add? During radical prostatectomy, urological surgeons have tried to identify the " cord-like NVB " at the lateral aspect of the prostate. However, little histological or physiological investigation was conducted to verify that the NVB identifi ed at surgery really included the cavernous nerve. Recently, there have been observations that refute the dogma that the cavernous nerve is always within the NVB.In this study, we have described a hammock-like distribution of the nerves on which the prostate rests, demonstrating that the NVB is more a network of multiple fi ne dispersed nerves than a distinct structure. We presented a novel nerve-sparing approach to complete hammock preservation. This risk-stratifi ed approach for determining the degree of nerve sparing based on the patient ' s likelihood of ipsilateral EPE seeks to categorize patients for optimal balance between oncological outcomes and functional outcomes. OBJECTIVES• To report the potency and oncological outcomes of patients undergoing robotassisted radical prostatectomy (RARP) using a risk-stratifi ed approach based on layers of periprostatic fascial dissection.• We also describe the surgical technique of complete hammock preservation or nerve sparing grade 1. PATIENTS AND METHODS• This is a retrospective study of 2317 patients who had robotic prostatectomy by a single surgeon at a single institution between January 2005 and June 2010.• Included patients were those with ≥ 1 year of follow-up and who were potent preoperatively, defi ned as having a sexual health inventory for men (SHIM) questionnaire score of > 21; thus, the fi nal number of patients in the study cohort was 1263.• Patients were categorized pre-operatively by a risk-stratifi ed approach into risk grades 1 -4, where risk grade 1 patients received nerve-sparing grade 1 or complete hammock preservation and so on for risk grades 2 -4, as long as intraoperative fi ndings permitted the planned nerve sparing.• We considered return to sexual function post-operatively by two criteria: i) ability to have successful intercourse (score of ≥ 4 on question 2 of the SHIM) and ii) SHIM > 21 or return to baseline sexual function. RESULTS• There was a signifi cant difference across different NS grades in terms of the percentages of patients who had intercourse and returned to baseline sexual function ( P < 0.001), with those that underwent NS grade 1 having the highest rates (90.9% and 81.7%) as compared to NS grades 2 (81.4% and74.3%), 3 (73.5% and 66.1%), and 4 (62% and 54.5%).• The overall positive surgical margin (PSM) rates for patients with NS grades 1, 2, 3, and 4 were 9.9%, 8.1%, 7.2%, and 8.7%, respectively ( P = 0.636).• The extraprostatic extension rates were 11.6%, 14.3%, 29.3%, and 36.2%, respectively ( P < 0.001).• Similarly, in patients younger than 60, intercourse and return to baseline sexual function rates were 94.9% and 84.3% for NS grade 1 as compared to 85.5% and 77.2% for NS grades 2, 76.9% and 69% for NS grades 3, and 64.8% and...
Study design: Prospective cross-sectional study. Objective: To study epidemiology, complication, neurological and functional outcome in nontraumatic spinal cord lesions (NTSCL) after inpatient rehabilitation. Setting: Neurological rehabilitation unit of a tertiary research hospital. Methods: Sixty-four patients (M/F ¼ 28:36) with NTSCL admitted from June 2005 to January 2008 for multidisciplinary rehabilitation. Epidemiology, medical complications during stay in rehabilitation, admission and dischargeFBarthel Index (BI) and American Spinal Injury Association (ASIA) impairment scale for functional and neurological recovery, respectively, were recorded and analyzed. Results: NTSCL constituted 60% (64 of 106) of the total SCL patients admitted for rehabilitation during the same period. Female patients outnumbered males (56.25%) in the study. Mean age, duration of illness and duration of stay in rehabilitation were 30.64±13.67 years (6-57), 7.09±9.15 months (1-48) and 55.75 ± 40.91 days (14-193), respectively. The ratio of paraplegia and quadriplegia was 2:1. Forty-four patients (68.75%) had incomplete cord lesion according to the ASIA impairment scale. Spinal tumors (26.6%) were found to be the most common etiology, followed by Pott's spine (25%) and transverse myelitis (22%). Urinary tract infection was found to be the most common complication (50%), followed by spasticity (35.93%) and urinary incontinence (31.25%). The mean BI scores showed significant (P ¼ 0.000) functional recovery during rehabilitation using paired Student's t-test. The ASIA impairment scale showed significant neurological recovery (P ¼ 0.001) using the Wilcoxon non-parametric test. Conclusions: NTSCL constitute a significant proportion of overall SCL. Female population, paraplegia and incomplete cord lesions are more common among NTSCL in this study. Patients with NTSCL recover significantly both neurologically and functionally with rehabilitation intervention.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.