gms | German Medical Science

Objective: HMGA2 is a gene regulating transcription factor associated with hypoxia, malignancy and poor prognosis in a glioblastoma. We compared the HMGA2 expression in border and central parts of the tumor and correlated these results with clinical parameters such as survival, age and MGMT-methylation status.

Methods: HMGA2 expression was determined by performing quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in a group of 26 glioblastoma patients and five non-tumorous brain specimens, which were used as controls. Intraoperatively tumor tissue specimen were extracted and differentiated into border and central parts. Border and central HMGA2 expressions were compared and analyzed by a Mann-Whitney U-Test. Correlations of gene expression with clinical parameters were calculated using Pearson’s rank correlation coefficient for qPCR and IHC data. The impact and prognostic value (Progression free Survival–PFS) of HMGA2 overexpression in the border zone of methylated and unmethylated glioblastomas was analyzed using the Kaplan-Meier method.

Results: Median age at diagnosis was 59.5±18 years. HMGA2 was generally increased in glioblastoma and significantly higher than in normal brain tissue (p=0.006, mean expression in glioblastoma 2.45; mean expression in normal brain tissue 0.04). Furthermore, HMGA2 expression in the border zone was significantly higher compared to the central parts using IHC (p=0.042; median border zone=8±7, median central zone=4±5). qPCR also showed a tendency to higher HMGA2 levels in the border zone compared to the tumor center, however, this difference was not significant (median tumor border=0.5±2; median central zone=0.37±0.9, p=0.297). Median PFS time was 8.5±3 months. A higher HMGA2 expression in the invasive border zone was associated with a decreased PFS (7.4 months). MGMT-methylated and non-methylated glioblastomas showed no significant differences (qPCR p=0.495; IHC p=0.892).

Conclusion: HMGA2 overexpression correlates with poor prognosis and malignancy of glioblastoma patients, independent from MGMT-methylation status. Furthermore, the results suggest that glioblastoma mark an emphasized overexpression of HMGA2 in the vital invasive border of the tumor and thus possibly making HMGA2 crucial for tumor invasiveness and aggressivity. Due to non-expression of HMGA2 in normal brain tissue, HMGA2 could be considered essential for future targeted therapies.