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01-06-2020 | Ovarian Cancer | Original Article

Histotype-specific analysis of acid ceramidase expression in ovarian cancer

Authors: Ahmed El-Balat, Thomas Karn, Uwe Holtrich, Sven Becker, Stefan Kommoss, Balázs Győrffy, Michael S. Anglesio, David G. Huntsman, Zacharias Drosos, Achim Rody, Heidrun Gevensleben, Lars C. Hanker

Published in: Virchows Archiv | Issue 6/2020

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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Title: Histotype-specific analysis of acid ceramidase expression in ovarian cancer
Authors: Ahmed El-Balat
Thomas Karn
Uwe Holtrich
Sven Becker
Stefan Kommoss
Balázs Győrffy
Michael S. Anglesio
David G. Huntsman
Zacharias Drosos
Achim Rody
Heidrun Gevensleben
Lars C. Hanker
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Ovarian Cancer
Ovarian Cancer
Estrogens
Published in: Virchows Archiv / Issue 6/2020
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02728-0

At a glance: The STEP trials

Springer Medicine

Histotype-specific analysis of acid ceramidase expression in ovarian cancer

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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