title: Acid ceramidase (AC)--a key enzyme of sphingolipid metabolism--correlates with better prognosis in epithelial ovarian cancer.
abstract: Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78-18.23] versus 18.1 mo (95% CI, 11.61-24.59; P=0.008) and 35.7 mo (95% CI, 22.24-47.16) versus 58.7 mo (95% CI, 36.48-80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13-3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.
authors.affiliation: Department of Obstetrics and Gynecology, University of Homburg, Homburg, Germany. hanker@med.uni-frankfurt.de
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Hanker
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
authors.forename: Uwe
authors.initials: U
authors.lastname: Holtrich
authors.forename: Regine
authors.initials: R
authors.lastname: Gätje
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.forename: Tomas
authors.initials: T
authors.lastname: Heinrich
authors.forename: Eugen
authors.initials: E
authors.lastname: Ruckhäberle
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
mesh_terms: D055573:Acid Ceramidase / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000401:mortality*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D013107:Sphingolipids / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D013107:Sphingolipids; D055573:Acid Ceramidase