Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients

J Neurosurg. 2012 Aug;117(2):204-11. doi: 10.3171/2012.4.JNS101702. Epub 2012 Jun 1.

Abstract

Object: In this paper, the authors' goal was to evaluate the prognostic value of YKL-40 expression as a prognostic factor for glioblastomas and to compare its validity to the already known MGMT.

Methods: Between January 2002 and January 2007, 105 patients were treated for cerebral glioblastoma. The extent of removal was classified in 4 groups. YKL-40 expression was evaluated by a semiquantitative immunohistochemical staining scale (0, no staining; 1, mild expression; and 2, strong expression). MGMT promoter methylation status was analyzed with methylation-specific polymerase chain reaction. All patients received adjuvant radiotherapy and chemotherapy. Kaplan-Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS), and to compare these parameters between the subgroups stratified by extent of surgical removal, MGMT methylation, and YKL-40 expression. The log-rank test was used to determine statistical significance. A multivariate regression analysis was applied to extent of removal, YKL-40 expression, and MGMT status to check their specific statistical power and to test the independence of the variables.

Results: There were 55 men and 50 women with a mean age of 58 years. Extent of surgical removal is reported. The MGMT promoter was methylated in 48 patients and nonmethylated in 57. Analysis of YKL-40 expression is reported. The median PFS was 10.7 months (14.9 months in the gross-total removal subgroup) (p < 0.0001), and the median OS was 12.5 months (17.4 months in the gross-total removal group) (p < 0.0001). In the univariate analysis, OS was significantly correlated to the extent of resection (p < 0.0001), MGMT status (p < 0.0001), and YKL-40 (p < 0.0001). Multivariate analysis showed that all 3 factors reached statistical significance with respect to patient survival. In particular, surgical removal contributed more than the 2 other factors to the survival prediction (β = -0.6254). Interestingly, YKL-40 (β = -0.3867) contributed more than MGMT (β = -0.1705) to the predicted survival.

Conclusions: The extent of removal is the most important factor influencing the OS of patients harboring glioblastomas. When biological aggressiveness is taken into account, YKL-40 expression was found to be an independent prognostic factor that predicts OS better than MGMT status.

Publication types

  • Comparative Study

MeSH terms

  • Adipokines / genetics*
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery*
  • Chitinase-3-Like Protein 1
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / surgery*
  • Humans
  • Immunoenzyme Techniques
  • Kaplan-Meier Estimate
  • Lectins / genetics*
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Tumor Suppressor Proteins / genetics*

Substances

  • Adipokines
  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes