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2022-RA-906-ESGO Acid ceramidase (ASAH1) expression is associated with improved progression- and overall survival in high-grade serous ovarian cancer patients
  1. Lars Christian Hanker1,
  2. Ahemd El-Balat2,
  3. Thomas Karn3,
  4. Uwe Holtrich3,
  5. Bendickt Decker1,
  6. Jakobus Pfisterer4,
  7. Heide Gevensleben5 and
  8. Stefan Kommoss6
  1. 1Gynecology and Obstetrics, Universityhospital Luebeck, Lübeck, Germany
  2. 2Gynecology and Obstetrics, Spital Ulster, Ulster, Switzerland
  3. 3Gynecology and Obstetrics, Universityhospital Frankfurt am Main, Frankfurt am Main, Germany
  4. 4Gynecology, Gynecologic Oncology Center, Kiel, Germany
  5. 5Institute of Pathology, University Hospital Bonn, Bonn, Germany
  6. 6Gynecology and Obstetrics, Universityhospital Tübingen, Tübingen, Germany


Introduction/Background Despite recent progress in the treatment of epithelial ovarian cancer the cure of this disease remains a challenge. Therefore new treatment options along with new prognostic and predictive makers are urgently needed. The enzyme acid ceramidase (AC) plays a central role in the sphingolipid network which is involved in tumorigenesis and progression. Furthermore AC directed therapies are currently under development. We investigated the expression of AC and its prognostic impact on ovarian cancers.

Methodology Patients of the AGO-cohort of the ICON-7 trial were analysed. In this randomized trial patients with advanced EOC received carboplatin+paclitaxel vs. carboplatin+paclitaxel+bevacizumab. Tissue micro arrays (TMAs) were constructed for performing immunohistochemical analysis of AC. The results were correlated with clinico-pathological characteristics and survival data.

Results Kaplan-Meier analysis (n=351) revealed that high levels of AC were associated with improved progression-free survival (PFS; 24.12 months [95% confidence interval (CI): 19.36 – 28.86] vs. 16.69 months [95% CI: 14.91 – 18.71], p < 0.0001) and overall-survival (OS; 66.83 months [95%CI: -] vs. 44.12 months [95%CI: 37.37 – 50.87], p < 0.0001). Subsequently, the prognostic value of AC expression together with clinical factors (i.e. FIGO stage, grading, histological subtype, bevacizumab medication and residual tumour burden after surgery) was further confirmed in multivariate Cox regression analysis in n= 426 patients (PFS: hazard ratio (HR) = 0.69 [95% CI: 0.550 – 0.877], p = 0.002; OS: HR = 0.67 [95%CI: 0.504 – 0.881], p = 0.004).

Conclusion Our data identify high levels of AC expression as a strong favorable prognostic marker in ovarian cancer patients.

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