gms | German Medical Science

Objective: Glioblastoma multiforme is the most common primary brain tumor. Despite intense research efforts worldwide, the prognosis of patients diagnosed with this tumor remains poor. Several clinical and molecular parameters influence overall survival. However, apart from IDH-1, a widely accepted prognostic marker that can be assessed immunohistochemically is still lacking. In this study the prognostic impact of several immunohistochemical markers was assessed in a cohort of 120 GBMs.

Method: In this study 120 tumor samples of patients diagnosed with glioblastoma multiforme underwent tissue microarray processing and subsequent immunohistochemical staining. All patients received adjuvant radiation and chemotherapy with an alkylating agent. The cellular expression of NogoA, OLIG2, GFAP, Ki67, p53 and IDH-1 (R132H) mutation as well as gender, surgical extent of resection and type of chemotherapy were assessed regarding their impact on overall survival, age and clinical status (KPS). Kaplan-Meier curve analysis (Gehan's Wilcoxon test), the independent two-sample t-test and multivariate analysis (Cox regression) were applied.

Results: A small group of patients with low GFAP expression levels showed a tendency towards younger age at the time of diagnosis, a finding yet not described in the literature. The detection of IDH-1 mutations did not show a significant prognostic impact, but a clear trend towards younger age (p=0.05063). Immunopositivity of p53 was significantly associated with longer overall survival in the Kaplan-Meier analysis (p=0.0480) and with younger age (p=0.04054) and better clinical status (p=0.01165). There was a strong trend towards longer overall survival of patients with lower expression levels of OLIG2, most pronounced at the cutoff at 30%, (p=0.0587). Interestingly, Cox regression analysis showed that expression rates of OLIG2 below 30% were a significant independent prognostic marker in glioblastoma multiforme (p=0.0168). The presence of p53 immunopositivity did not reach statistical significance in the multivariate analysis.

Conclusions: In conclusion, the percentage of OLIG2 expressing tumor cells emerged as a prognostic factor for overall survival. Further studies are necessary to reveal the exact role of OLIG2 in gliomagenesis.