Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy.

ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of TMPRSS2:ERG fusion, higher Ki67-labeling index and PTEN deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64-2.10, p < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11-1.49, p = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse.

Oncotarget. 2019 Aug 13*** epublish ***

Cornelia Schroeder, Elham Navid-Hill, Jan Meiners, Claudia Hube-Magg, Martina Kluth, Georgia Makrypidi-Fraune, Ronald Simon, Franziska Büscheck, Andreas M Luebke, Cosima Goebel, Dagmar S Lang, Sören Weidemann, Emily Neubauer, Andrea Hinsch, Frank Jacobsen, Patrick Lebok, Uwe Michl, Dirk Pehrke, Hartwig Huland, Markus Graefen, Thorsten Schlomm, Guido Sauter, Doris Höflmayer

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.