Specific Detection of Prostate Cancer Cells in Urine by RNA In Situ Hybridization

No AccessJournal of UrologyAdult Urology1 Jul 2021Specific Detection of Prostate Cancer Cells in Urine by RNA In Situ Hybridization Jillian N. Eskra, Daniel Rabizadeh, Jiayi Zhang, William B. Isaacs, Jun Luo, and Christian P. Pavlovich Jillian N. EskraJillian N. Eskra The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author , Daniel RabizadehDaniel Rabizadeh The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author , Jiayi ZhangJiayi Zhang The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author , William B. IsaacsWilliam B. Isaacs The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author , Jun LuoJun Luo *Correspondence: The Brady Urological Institute, The Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, Maryland 21287 telephone: 443-287-5625; E-mail Address: [email protected] or telephone: 410-550-3338; E-mail Address: [email protected] The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author , and Christian P. PavlovichChristian P. Pavlovich *Correspondence: The Brady Urological Institute, The Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, Maryland 21287 telephone: 443-287-5625; E-mail Address: [email protected] or telephone: 410-550-3338; E-mail Address: [email protected] The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland Recipient of Patrick C. Walsh Foundation intramural grant for prostate cancer research. More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001691AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Noninvasive tests that can accurately detect prostate cancer are urgently needed for prostate cancer diagnosis, surveillance and prognosis. Exfoliated prostate cells captured in urine represent a promising resource for noninvasive detection of prostate cancer. We investigated performance of a novel cell-based urine test for detection of clinically significant prostate cancer. Materials and Methods: We previously developed a multiplex RNA in situ hybridization assay targeting NKX3-1, PRAC1 and PCA3 that enables identification and quantification of malignant and benign prostate cells released into urine. We investigated application of the assay for prostate cancer detection in a cohort of 98 patients suspected of harboring prostate cancer. Urine was collected following digital rectal examination, and the sediment was isolated and evaluated by RNA in situ hybridization. Samples were scored based on cellular expression of RNA in situ hybridization targets. Cells of prostate origin were defined by positivity for NKX3-1 and/or PRAC1, and prostate cancer cells by positivity for PCA3. Results: Prostate cells (NKX3-1/PRAC1+ cells) were detected in 69 samples, among which 20 were positive for PCA3 (ie positive for prostate cancer cells). Comparison of RNA in situ hybridization results with biopsy outcome and clinical variables revealed that positivity for cancer by RNA in situ hybridization significantly correlated with intermediate/high risk cancer (p=0.003), PSA density (p=0.022), significant disease (p <0.0001) and Gleason score (p=0.003). The test was 95% specific and 51% sensitive for detection of clinically significant prostate cancer. Conclusions: Identification of exfoliated prostate cancer cells in urine by RNA in situ hybridization provides a novel tool for highly specific and noninvasive detection of prostate cancer. References 1. : All change in the prostate cancer diagnostic pathway. Nat Rev Clin Oncol 2020; 17: 372. Google Scholar 2. : Complications after systematic, random, and image-guided prostate biopsy. Eur Urol 2017; 71: 353. Google Scholar 3. : Trends in management for patients with localized prostate cancer, 1990-2013. JAMA 2015; 314: 80. Google Scholar 4. : Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part I: risk stratification, shared decision making, and care options. J Urol 2018; 199: 683. Link, Google Scholar 5. : Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014; 65: 1046. Google Scholar 6. : Addressing the need for repeat prostate biopsy: new technology and approaches. Nat Rev Urol 2015; 12: 435. 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Link, Google Scholar Disclosure: Eskra, Isaacs, Pavlovich and Luo are named inventors on a patent application filed by Johns Hopkins University relating to the RISH assay used in this article. Supported by the Patrick C. Walsh Research Fund and Johns Hopkins Prostate Cancer SPORE P50 CA058236. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue 1July 2021Page: 37-43Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordsurinecell biologyin situ hybridizationprostatic neoplasmsbiomarkersAcknowledgmentsThe authors thank Drs. Alan Meeker and Christopher Heaphy for helpful discussions, and the Brady Urological Institute Biorepository team for assistance in sample collection.MetricsAuthor Information Jillian N. Eskra The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author Daniel Rabizadeh The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author Jiayi Zhang The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author William B. Isaacs The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland More articles by this author Jun Luo The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland *Correspondence: The Brady Urological Institute, The Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, Maryland 21287 telephone: 443-287-5625; E-mail Address: [email protected] or telephone: 410-550-3338; E-mail Address: [email protected] More articles by this author Christian P. Pavlovich The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland *Correspondence: The Brady Urological Institute, The Johns Hopkins School of Medicine, 600 N. Wolfe St., Baltimore, Maryland 21287 telephone: 443-287-5625; E-mail Address: [email protected] or telephone: 410-550-3338; E-mail Address: [email protected] Recipient of Patrick C. Walsh Foundation intramural grant for prostate cancer research. More articles by this author Expand All Disclosure: Eskra, Isaacs, Pavlovich and Luo are named inventors on a patent application filed by Johns Hopkins University relating to the RISH assay used in this article. Supported by the Patrick C. Walsh Research Fund and Johns Hopkins Prostate Cancer SPORE P50 CA058236. Advertisement PDF downloadLoading ...