Abstract
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.
Highlights
In Western societies, prostate cancer is the most prevalent cancer in males [1]
ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of prostate specific antigen (PSA) recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy
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
Summary
In Western societies, prostate cancer is the most prevalent cancer in males [1]. Most of these are indolent and only about 10% are highly aggressive. The ELAC2 gene (alias RNase Z2, Hereditary Prostate Cancer locus 2 (HPC2)), located at chromosome 17p12, encodes a zinc phosphodiesterase. ELAC2 is of particular interest in prostate cancer because sequence variants of this gene have been suggested to play a role in genetic susceptibility to hereditary and sporadic forms of the disease [8,9,10,11,12,13]. Studies assessing the expression profile and putative prognostic role of the ELAC2 protein in prostate cancer are lacking
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