Protein Expression Profiles among Lichen Sclerosus Urethral Strictures—Can Urethroplasty Success be Predicted?

No AccessJournal of UrologyAdult Urology1 Apr 2020Protein Expression Profiles among Lichen Sclerosus Urethral Strictures—Can Urethroplasty Success be Predicted?This article is commented on by the following:Editorial Comment Alison C. Levy, Matthew Moynihan, Jennifer A. Bennett, Travis Sullivan, Kristian Stensland, Brendan M. Browne, Ariel Fredrick, Jaime A. Cavallo, Elizabeth Pagura, Rafael Tua-Caraccia, Kimberly M. Rieger-Christ, and Alex J. Vanni Alison C. LevyAlison C. Levy Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Matthew MoynihanMatthew Moynihan Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Jennifer A. BennettJennifer A. Bennett Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Travis SullivanTravis Sullivan Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Kristian StenslandKristian Stensland Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Brendan M. BrowneBrendan M. Browne Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Ariel FredrickAriel Fredrick Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Jaime A. CavalloJaime A. Cavallo Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , Elizabeth PaguraElizabeth Pagura Tufts University School of Medicine, Boston, Massachusetts More articles by this author , Rafael Tua-CaracciaRafael Tua-Caraccia Tufts University School of Medicine, Boston, Massachusetts More articles by this author , Kimberly M. Rieger-ChristKimberly M. Rieger-Christ Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author , and Alex J. VanniAlex J. Vanni *Correspondence: Department of Urology, Lahey Hospital and Medical Center, 41 Mall Rd., Burlington, Massachusetts 01805 telephone: 781-744-8420; FAX: 781-744-5429; E-mail Address: [email protected] Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000610AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Urethroplasty of lichen sclerosus strictures has a significantly higher failure rate than strictures due to other causes. We sought to determine predictors of urethroplasty failure in men with lichen sclerosus urethral stricture disease by evaluating protein expression profiles. Materials and Methods: Urethral tissue was excised from patients with lichen sclerosus who were undergoing urethroplasty of urethral stricture disease at a single institution. A tissue microarray was created with cores from each sample. Immunohistochemistry was performed to compare protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. Stricture recurrence was defined by the need for a subsequent unanticipated procedure for urethral stricture disease. Results: We evaluated 50 men with lichen sclerosus urethral stricture disease, including 31 with successful reconstruction and 19 with recurrent stricture. Recurrent strictures expressed lower levels of several inflammatory markers and had a lower Ki-67 mitotic index and significantly higher vascular endothelial growth factor levels than nonrecurrent strictures. Conclusions: To our knowledge this is the first study to use tissue protein expression to identify risk factors for urethroplasty failure among men with lichen sclerosus urethral stricture disease. Our findings suggest that recurrent lichen sclerosus strictures demonstrate a suppressed inflammatory response, a decreased cell turnover rate, and poor oxygenation and nutrient delivery. Prospective studies are needed to clarify the role of these pathways in the pathophysiology of lichen sclerosus urethral stricture disease, determine whether preoperative biopsy can predict urethroplasty success, help counsel patients and develop future treatments. References 1. : Insights into the pathophysiology of urethral stricture disease due to lichen sclerosus: comparison of pathological markers in lichen sclerosus induced strictures vs nonlichen sclerosus induced strictures. J Urol 2019; 201: 1158. 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Google Scholar The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by the Robert E. Wise Research and Education Institute. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Editor's Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 843 and 844. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology7 Jan 2020Editorial Comment Volume 203Issue 4April 2020Page: 773-778 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.Keywordsprotein array analysislichen sclerosus et atrophicusrisk factorsrecurrenceurethral strictureAcknowledgmentSlides and blocks were sent to the Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland for TMA creation. Stains other than those for p53, Ki-67, cyclin D1 and p16 were reviewed by a pathologist at Pathline Emerge, Ramsey, New Jersey. HPV analysis was performed at ProPath®, Dallas, Texas.MetricsAuthor Information Alison C. Levy Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Matthew Moynihan Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Jennifer A. Bennett Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Travis Sullivan Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Kristian Stensland Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Brendan M. Browne Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Ariel Fredrick Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Jaime A. Cavallo Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Elizabeth Pagura Tufts University School of Medicine, Boston, Massachusetts More articles by this author Rafael Tua-Caraccia Tufts University School of Medicine, Boston, Massachusetts More articles by this author Kimberly M. Rieger-Christ Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Alex J. Vanni Lahey Hospital and Medical Center, Burlington, Massachusetts *Correspondence: Department of Urology, Lahey Hospital and Medical Center, 41 Mall Rd., Burlington, Massachusetts 01805 telephone: 781-744-8420; FAX: 781-744-5429; E-mail Address: [email protected] More articles by this author Expand All The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by the Robert E. Wise Research and Education Institute. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Editor's Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 843 and 844. Advertisement PDF downloadLoading ...