Correlation of acid ceramidase (AC), a key enzyme of the sphingolipid metabolism, with prognosis in epithelial ovarian cancer.

Abstract

e15562 Background: Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, plays an important role in cancer progression. Objective of this study was to explore the expression of AC in ovarian cancer and its relationship with prognosis. Methods: The expression of AC in n=119 ovarian cancer patients was determined by immunohistochemistry and correlated to clinical and pathological characteristics as well as survival. Results: Low AC expression was independently associated with reduced progression-free survival of 14 (CI95%: 9.20-18.8) vs. 19.6 (CI95%: 11.1-28.1) months (p=0.004) as well as reduced overall survival of 41.2 (CI95%: 30.7-51.7) months versus 58.1 (CI 95%: 34.6-81.6) months (p=0.096). In multivariate analysis AC presents as independent prognostic factor for PFS (HR 1.70; CI95%: 1.00-2.88, p=0.05) and OS (HR 1.44; CI95%: 0.80-2.62, P=0.23). Conclusions: Acid ceramidase is an independant prognostic factor in epithelial ovarian cancer. Low AC expression is associated with tumour progression in ovarian carcinoma. These results are in contrast to the concept of AC as an promoter for tumor progression, but are supported by the tumour-suppressing and proapoptotic function of the enzymatic product of AC, i.e. sphingosine (SPH) in various cancer types.