High levels of phosphorylated MAP kinase are associated with poor survival among patients with glioblastoma during the temozolomide era
Neuro-Oncology, 01/04/2013

Patil CG et al. – This study provides quantitative means of evaluating p-MAPK in patients with GBM. It confirms the significant and independent prognostic relevance of p-MAPK in predicting survival of patients with GBM treated in the temozolomide era and highlights the need for therapies targeting the p-MAPK oncogenic pathway.
Methods

• Nuclear p-MAPK expression of 108 patients with GBM was quantified and categorized in the following levels: low (0%–10%), medium (11%–40%), and high (41%–100%).
• Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model.
• Our study included 108 patients with newly diagnosed GBM. Median age was 65 years, and 74% had high Karnofsky performance status (KPS ? 80).

Results

• Median overall survival among all patients was 19.5 months.
• Activated MAPK expression levels of <10%, 11%–40%, and ?41% were observed in 33 (30.6%), 37 (34.3%), and 38 (35.2%) patients, respectively.
• Median survival for low, medium, and high p-MAPK expression was 32.4, 18.2, and 12.5 months, respectively.
• Multivariate analysis showed 2.4-times hazard of death among patients with intermediate p-MAPK than low p-MAPK expression (hazard ratio [HR], 2.4; P = .02); high-expression patients were 3.9 times more likely to die, compared with patients with low p-MAPK (HR, 3.9; P = .007). Patients aged ?65 years (HR, 2.8; P = .002) with KPS < 80 (HR, 3.1; P = .0003) and biopsy or partial resection (HR, 1.9; P = .02) had higher hazard of death.
• MGMT and PTEN expression were not associated with survival differences.