PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance

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Lokman , U , Erickson , A M , Vasarainen , H , Rannikko , A S & Mirtti , T 2018 , ' PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance ' , European Urology Focus , vol. 4 , no. 6 , pp. 867-873 . https://doi.org/10.1016/j.euf.2017.03.004

Title: PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance
Author: Lokman, Utku; Erickson, Andrew M.; Vasarainen, Hanna; Rannikko, Antti S.; Mirtti, Tuomas
Contributor organization: Urologian yksikkö
Department of Surgery
Clinicum
Institute for Molecular Medicine Finland
University of Helsinki
Department of Pathology
Medicum
HUSLAB
HUS Abdominal Center
Date: 2018-12
Language: eng
Number of pages: 7
Belongs to series: European Urology Focus
ISSN: 2405-4569
DOI: https://doi.org/10.1016/j.euf.2017.03.004
URI: http://hdl.handle.net/10138/299163
Abstract: Background Active surveillance (AS) is an option for men with low-risk prostate cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa progression and survival. Objective To study the role of ERG and PTEN status in the Prostate Cancer Research International: Active Surveillance (PRIAS) trial diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse surgical findings in subsequent radical prostatectomy (RP). Design, setting, and participants A total of 231 patients were recruited to the PRIAS between 2007 and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections were stained with ERG and PTEN antibodies, and scored as either negative or positive. Outcome measurements and statistical analyses Outcomes were followed up by biopsy GG upgrade (GG ≥ 2) and protocol-based treatment change, as well as adverse findings in RP (GG ≥ 3 or pathological stage ≥ 3). Clinical variables and biomarker status in DBx were correlated in Cox regression analysis and cumulative survival in Kaplan–Meier analysis, and finally, Gray’s competing risk analysis was performed and nonprotocol-based discontinuation was considered as a competing event. Results and limitations In both uni- and multivariate Cox regression analyses, only the number of positive cores in the DBx, the number of rebiopsy sessions, and PTEN status at diagnosis were significantly associated with rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In Kaplan–Meier analysis, PTEN loss was associated with a shorter time to GG upgrade and treatment change. Patients with PTEN loss had a higher probability for protocol-based discontinuation but not for competing risk factors compared with patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG status, while PTEN was not. Limitations include a retrospective analysis of prospective cohort data. Conclusions PTEN status at diagnosis is a potential biomarker for identifying patients with PCa on AS with a high risk for progression or adverse findings on subsequent RP. Patient summary A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression. Keywords PTEN; ERG; Immunohistochemistry; Biopsy; Active surveillance
Subject: 3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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