Artikel
ALDH1A1 as a molecular marker with better prognosis for glioblastoma patients
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been identified in a variety of human cancers to be expressed by tumor cells and to serve as a reliable marker to predict patients clinical outcome. However, little is known so far about the function of ALDH1A1 in malignant brain tumors.
Methods: We analyzed the expression of ALDH1A1 protein in developing and mature cerebral and cerebellar tissue as well as in a series of 93 cases of primary glioblastoma. Tissue samples for histopathological diagnosis and molecular genetic analysis were acquired either via microsurgical tumor resection (n = 56) or stereotactical serial biopsy (n = 37). Tumor diagnoses were established based on the criteria of the latest WHO brain tumor classification. Patients were treated mainly with radiochemotherapy followed by adjuvant temozolomide chemotherapie according to the EORTC/NCIC protocol. In case of tumor recurrence, salvage treatment was rendered by our institutional guidelines and on a personalized cancer therapy basis.
Results: While ALDH1A1 was absent in the stem cell niches at varying stages of CNS development, strong ALDH1A1 expression was observed in mature astrocytes, coexpressing GFAP and S100. 92/93 (99%) of the examined glioblastoma cases showed ALDH1A1 expression in up to 49% of tumor cells. The majority of these cells co-expressed GFAP, but not stem cell markers, such as Nestin, OLIG2 or SOX2. Finally, strong expression of ALDH1A1 detected by immunhistochemistry correlated with a significantly better overall survival of the patients and proved to be a prognostic marker (p < 0.01), independent of the MGMT promoter methylation status (p = 0.024) and the age of the patient (p = 0.024).
Conclusions: We suggest ALDH1A1 as a marker of astrocytic differentiation and of better prognosis in patients suffering from glioblastomas.