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

No AccessJournal of UrologyAdult Urology1 Jun 2019Insights into the Pathophysiology of Urethral Stricture Disease due to Lichen Sclerosus: Comparison of Pathological Markers in Lichen Sclerosus Induced Strictures vs Nonlichen Sclerosus Induced StricturesThis article is commented on by the following:Editorial CommentEditorial Comment Alison Levy, Brendan Browne, Ariel Fredrick, Kristian Stensland, Jennifer Bennett, Travis Sullivan, Kimberly M. Rieger-Christ, and Alex J. Vanni Alison LevyAlison Levy Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts , Brendan BrowneBrendan Browne Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts , Ariel FredrickAriel Fredrick Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts , Kristian StenslandKristian Stensland Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts , Jennifer BennettJennifer Bennett Department of Pathology, Lahey Hospital and Medical Center, Burlington, Massachusetts , Travis SullivanTravis Sullivan Department of Translational Research, Lahey Hospital and Medical Center, Burlington, Massachusetts , Kimberly M. Rieger-ChristKimberly M. Rieger-Christ Department of Translational Research, Lahey Hospital and Medical Center, Burlington, Massachusetts , and Alex J. VanniAlex J. Vanni *Correspondence: Department of Urology, Lahey Hospital and Medical Center, 41 Mall Rd., Burlington, Massachusetts 01805 (telephone: 781-744-2508; FAX: 781-744-5429; e-mail: E-mail Address: [email protected]). Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts View All Author Informationhttps://doi.org/10.1097/JU.0000000000000155AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated the pathophysiology of lichen sclerosus and nonlichen sclerosus urethral stricture disease by comparing protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. Materials and Methods: Tissue samples were collected from the urethral strictures of 81 patients undergoing urethroplasty. Clinical and demographic data were obtained by chart review. After identifying areas pathognomonic for lichen sclerosus a tissue microarray was created with cores from each sample and immunohistochemistry was performed. Results: Patients had similar baseline demographics and comorbidities. Of the 81 strictures 58 were and 23 were not due to lichen sclerosus. Lichen sclerosus strictures were significantly longer and showed higher levels of inflammation. The proportion of T cells which stained positive for CD8 was significantly higher in strictures due to lichen sclerosus (50% vs 13%, p = 0.004). CCL-4 was expressed significantly more in strictures due to lichen sclerosus (76% vs 42%, p = 0.01). Several other inflammatory markers were only found in strictures due to lichen sclerosus. Block-like p16, a surrogate for high risk human papillomavirus infection, and varicella zoster virus were found only in lichen sclerosus urethral stricture disease samples, although both were rare. Epstein-Barr virus RNA was found in significantly more lichen sclerosus samples (37% vs 10%, p = 0.024). Conclusions: To our knowledge this is the first study to evaluate protein expression in lichen sclerosus urethral stricture disease. These strictures demonstrate increased inflammation compared to nonlichen sclerosus urethral strictures. Markers of oxidative stress, cell cycle dysregulation and the androgen receptor do not appear to be uniquely associated with lichen sclerosus urethral stricture disease. Positive staining for several viruses in samples of lichen sclerosus urethral stricture disease suggests a possible infectious etiology. References 1. : Outcomes for management of lichen sclerosus urethral strictures by 3 different techniques. Urology 2016; 91: 215. Google Scholar 2. : Understanding the relationship between chronic systemic disease and lichen sclerosus urethral strictures. J Urol 2016; 195: 363. 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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 R. E. Wise Research and Education Institute. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. © 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLevy A, Moynihan M, Bennett J, Sullivan T, Stensland K, Browne B, Fredrick A, Cavallo J, Pagura E, Tua-Caraccia R, Rieger-Christ K and Vanni A (2019) Protein Expression Profiles among Lichen Sclerosus Urethral Strictures—Can Urethroplasty Success be Predicted?Journal of Urology, VOL. 203, NO. 4, (773-778), Online publication date: 1-Apr-2020.Related articlesJournal of Urology13 Mar 2019Editorial CommentJournal of Urology13 Mar 2019Editorial Comment Volume 201Issue 6June 2019Page: 1158-1163Supplementary Materials Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.KeywordspathologyinflammationEpstein-Barr virus infectionslichen sclerosus et atrophicusurethral strictureAcknowledgementsDrs. Jason Badrinarain and Jorge Yao, Pathline Emerge, Ramsey, New Jersey, were study collaborators. TMAs were created at the Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland. HPV analysis of block-like p16 staining samples was done at ProPath®, Dallas, Texas.MetricsAuthor Information Alison Levy Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Brendan Browne Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Ariel Fredrick Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Kristian Stensland Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Jennifer Bennett Department of Pathology, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Travis Sullivan Department of Translational Research, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Kimberly M. Rieger-Christ Department of Translational Research, Lahey Hospital and Medical Center, Burlington, Massachusetts More articles by this author Alex J. Vanni Department of Urology, Lahey Hospital and Medical Center, Burlington, Massachusetts *Correspondence: Department of Urology, Lahey Hospital and Medical Center, 41 Mall Rd., Burlington, Massachusetts 01805 (telephone: 781-744-2508; FAX: 781-744-5429; e-mail: 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 R. E. Wise Research and Education Institute. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Advertisement PDF downloadLoading ...