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Histotype-specific analysis of acid ceramidase expression in ovarian cancer

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Abstract

Acid ceramidase (ASAH1) is a key player in sphingolipid metabolism and signaling. It has prognostic value for several cancers, but histotype-specific analyses of ovarian cancer are not yet available. We used three retrospective TMA cohorts encompassing a total of 1106 ovarian cancers with follow-up data for immunohistochemical analysis of acid ceramidase (ASAH1) expression. Patients with sub-optimal debulking and persistent residual tumor after surgery introduced bias in the prognostic analysis and were excluded from further studies. Overall, we detected an association of ASAH1 expression with better prognosis in ovarian cancer patients. ASAH1 expression differed between histological ovarian cancer histotypes with most frequent expression in endometrioid and clear cell ovarian cancer, which are both associated with good prognosis. Stratified subgroup analyses within these histotypes did not reveal significant survival differences, but the power of the analysis may be limited by smaller sample sizes. In contrast to breast cancer, we found only a modest concordance between estrogen receptor status and ASAH1 expression within the endometrioid ovarian cancer histotype. In an exploratory analysis of estrogen receptor negative endometrioid ovarian cancer, ASAH1 expression was associated with significantly better overall survival (P = 0.007). Acid ceramidase is most frequently expressed in endometrioid and clear cell histotypes and could add independent prognostic value to estrogen receptor in endometrioid ovarian cancer. Modulating sphingolipid metabolism may lead to novel therapeutic intervention strategies for this disease.

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Funding

This work was supported by grants from the H.W. & J. Hector Stiftung, Weinheim (grant number M82) and the Margarete-Bonifer-Stiftung, Bad Soden.

Author information

Authors and Affiliations

  1. Goethe University Frankfurt, Department of Obstetrics and Gynecology, Frankfurt, Germany

    Ahmed El-Balat, Thomas Karn, Uwe Holtrich & Sven Becker

  2. Department of Woman’s Health, Tuebingen University Hospital, Tuebingen, Germany

    Stefan Kommoss

  3. MTA TTK Lendület Cancer Biomarker Research Group & Semmelweis, University Second Department of Pediatrics, Budapest, Hungary

    Balázs Győrffy

  4. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada

    Michael S. Anglesio & David G. Huntsman

  5. Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, Canada

    David G. Huntsman

  6. Gynecology and Obstetrics, University Hospital Lübeck, Lübeck, Germany

    Zacharias Drosos, Achim Rody & Lars C. Hanker

  7. Institute of Pathology, University Hospital Bonn, Bonn, Germany

    Heidrun Gevensleben

Authors
  1. Ahmed El-Balat
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  2. Thomas Karn
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  3. Uwe Holtrich
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  12. Lars C. Hanker
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Contributions

ZD, LH, and AR designed the study. DH, MA, and SK provided tumor samples and clinical data. UH performed immunohistochemical analyses of the samples and coordinated the study conduct. HG evaluated and scored stained tissue slides and helped finalizing the manuscript. TK and BG carried out the statistical analyses and interpreted the data. AEB, UH, TK, and SB drafted and finalized the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Ahmed El-Balat.

Ethics declarations

Collection of patient specimens and data from the British Columbia cohort was done under approved research protocols reviewed by the British Columbia Cancer Agency and University of British Columbia research ethics board (H05–60119).

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The authors declare that they have no conflicts of interest.

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El-Balat, A., Karn, T., Holtrich, U. et al. Histotype-specific analysis of acid ceramidase expression in ovarian cancer. Virchows Arch 476, 855–862 (2020). https://doi.org/10.1007/s00428-019-02728-0

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  • DOI: https://doi.org/10.1007/s00428-019-02728-0

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