title: Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer.
abstract: Acid ceramidase (ASAH1) a key enzyme of sphingolipid metabolism converting pro-apoptotic ceramide to sphingosine has been shown to be overexpressed in various cancers. We previously demonstrated higher expression of ASAH1 in ER positive compared to ER negative breast cancer. In the current study we performed subtype specific analyses of ASAH1 gene expression in invasive and non invasive breast cancer. We show that expression of ASAH1 is mainly associated with luminal A - like cancers which are known to have the best prognosis of all breast cancer subtypes. Moreover tumors with high ASAH1 expression among the other subtypes are also characterized by an improved prognosis. The good prognosis of tumors with high ASAH1 is independent of the type of adjuvant treatment in breast cancer and is also detected in non small cell lung cancer patients. Moreover, even in pre-invasive DCIS of the breast ASAH1 is associated with a luminal phenotype and a reduced frequency of recurrences. Thus, high ASAH1 expression is generally associated with an improved prognosis in invasive breast cancer independent of adjuvant treatment and could also be valuable as prognostic factor for pre-invasive DCIS.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sänger
authors.affiliation: Department of Obstetrics and Gynecology, Heinrich-Heine-University Duesseldorf, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Ruckhäberle
authors.affiliation: MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary; 2(nd) Dept. of Pediatrics, Semmelweis University, Budapest, Hungary; MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Györffy
authors.affiliation: Zentrum für Pathologie, Zytologie und Molekularpathologie Neuss, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Heinrich
authors.affiliation: Department of Obstetrics and Gynecology, Heinrich-Heine-University Duesseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Graf
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Holtrich
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany. Electronic address: t.karn@em.uni-frankfurt.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
mesh_terms: D055573:Acid Ceramidase / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015996:Survival Rate
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase
keywords: Acid ceramidase; Breast cancer; Ceramide; Ductal carcinoma in situ; Prognosis; Sphingolipids