title: ALDH1A1 is a marker of astrocytic differentiation during brain development and correlates with better survival in glioblastoma patients.
abstract: Glioblastoma is the most common malignant brain tumor and patients usually succumb to their disease within 2 years. Aldehyde dehydrogenase 1A1 (ALDH1A1) has been suggested as a marker for cancer stem cells that is associated with poor prognosis in human gliomas. However, little is known about the expression and the function of ALDH1A1 in early stages of brain development. We analyzed ALDH1A1 expression in developing and mature central nervous system (CNS) as well as in 93 cases of primary glioblastomas. Surprisingly, ALDH1A1 was absent in the stem cell niches at varying stages of CNS development, but strong ALDH1A1 expression was observed in mature astrocytes coexpressing GFAP and S100. There were 92 out of 93 glioblastomas (99%) that showed ALDH1A1 protein expression in up to 49% of tumor cells. The majority of these cells co-expressed GFAP, but not established stem cell markers such as Nestin, OLIG2 or SOX2. Finally, strong expression of ALDH1A1 correlated with a significantly better survival of the patients and proved to be an independent prognostic marker in our series (P < 0.01). In contrast to other published data, we therefore provide evidence for ALDH1A1 as a marker of astrocytic differentiation during brain development and of better prognosis in patients suffering from primary glioblastoma.
authors.affiliation: Center for Neuropathology and Prion Research, Munich, Germany.
authors.forename: S Alexandra
authors.initials: SA
authors.lastname: Adam
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Julia
authors.initials: J
authors.lastname: Pöschl
authors.forename: Sabina
authors.initials: S
authors.lastname: Eigenbrod
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D001253:Astrocytes / Q000166:cytology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D002454:Cell Differentiation / Q000502:physiology; D018572:Disease-Free Survival; D005333:Fetus; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D055495:Neurogenesis / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055153:Stem Cell Niche / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase