Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer

Publication date: Available online 22 July 2019Source: European UrologyAuthor(s): Alec Paschalis, Beshara Sheehan, Ruth Riisnaes, Daniel Nava Rodrigues, Bora Gurel, Claudia Bertan, Ana Ferreira, Maryou B.K. Lambros, George Seed, Wei Yuan, David Dolling, Jon C. Welti, Antje Neeb, Semini Sumanasuriya, Pasquale Rescigno, Diletta Bianchini, Nina Tunariu, Suzanne Carreira, Adam Sharp, Wim OyenAbstractBackgroundProstate-specific membrane antigen (PSMA; folate hydrolase) prostate cancer (PC) expression has theranostic utility.ObjectiveTo elucidate PC PSMA expression and associate this with defective DNA damage repair (DDR).Design, setting, and participantsMembranous PSMA (mPSMA) expression was scored immunohistochemically from metastatic castration-resistant PC (mCRPC) and matching, same-patient, diagnostic biopsies, and correlated with next-generation sequencing (NGS) and clinical outcome data.Outcome measurements and statistical analysisExpression of mPSMA was quantitated by modified H-score. Patient DNA was tested by NGS. Gene expression and activity scores were determined from mCRPC transcriptomes. Statistical correlations utilised Wilcoxon signed rank tests, survival was estimated by Kaplan-Meier test, and sample heterogeneity was quantified by Shannon's diversity index.Results and limitationsExpression of mPSMA at diagnosis was associated with higher Gleason grade (p = 0.04) and worse overall survival (p = 0.006). Overall, mPSMA expression levels increased ...
Source: European Urology - Category: Urology & Nephrology Source Type: research

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