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.