gms | German Medical Science

Objective: Recently, cytosolic ALDH1A1 has been identified as a marker of stem cell characteristics and temozolomide resistance in glioblastoma tumor cells. In a small series of patients ALDH1A1 expression level was prognostic with regard to overall survival independent of MGMT methylation status. The present study aimed to confirm this result in a larger cohort of patients.

Method: Paraffin embedded tumor tissue from 5 neurosurgical / neuropathology departments together with clinical data were collected. Tumors were immunohistochemically stained against cytosolic ALDH1A1 and the percentage of cells expressing ALDH1A1 was quantified. Furthermore MGMT promotor methylation status was assessed by specific relative real-time PCR (MethyQESD).

Results: Data could be gathered for 188 cases. All patients underwent surgical tumor resection and most radiochemotherapy according to the Stupp protocol. Median overall survival of the GB patient cohort was 15.6 months (range; 0.3-86.7). A significant cut-off for ALDH1A1 expression could be identified at 0.1. Best survival was observed for the patient group with MGMT >0.8 / ALDH1A1 ≤0.1 and in descending order of survival for MGMT >0.8 / ALDH1A1 >0.1, MGMT ≤0.8 / ALDH1A1 ≤0.1 and worst survival for MGMT ≤0.8 / ALDH1A1 >0.1 (log-rank test 0.002). In a multivariate analysis including age and preoperative KPS, ALDH1A1 expression level and MGMT level remain significant factors influencing overall survival.

Conclusions: The present data confirm that ALDH1A1 represents an MGMT independent prognostic factor for survival in glioblastoma patients following resection and radiochemotherapy. A cut-off value of ALDH1A1 expression of 0.1 could be identified. The underlying mechanism of the negative prognostic value of a higher ALDH1A1 expression could be a resistance to temozolomide in ALDH1A1 positive cells. This is supported by the fact that most recurrent tumors show an increased ALDH1A1 expression in comparison to the corresponding primary tumors.