Evaluation and Prognostic Significance of ACATI as a Marker of Prostate Cancer Progression

INTRODUCTION Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. METHODSIn the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. RESULTSUsing quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P<0.0001), in Gleason score (GS) 8 cancers versus GS6 cancers (P<0.0001), GS8 cancers versus GS7 cancers (P=0.001), as well as pT3/pT4 versus pT2 cancers (P=0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI=1.13-2.9, P=0.0128), and multivariate models (HR, 1.69, CI=1.01-2.81, P=0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P=0.0025), whereas ERG positive cases did not display any differences. DISCUSSIONTaken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. Prostate 74:372-380, 2014. (c) 2013 Wiley Periodicals, Inc.