A study of clinico-pathological parameters and O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation status in the prognostication of gliosarcoma

Neuropathology. 2012 Oct;32(5):534-42. doi: 10.1111/j.1440-1789.2012.01297.x. Epub 2012 Mar 1.

Abstract

Gliosarcoma is a rare variant of glioblastoma multiforme (GBM) with similar clinical presentation and prognosis but a distinct genetic profile. The clinicopathological features of 22 cases of gliosarcoma were analyzed with respect to age, sex, KPS score, operative diagnosis, extent of resection and histopathological subtype (predominantly sarcomatous [PS], predominantly gliomatous [PG] or mixed). Twelve cases were PS, six were PG and four were mixed. The histological subtype did not correlate with the operative diagnosis; however, it did significantly correlate with the extent of resection (P=0.014). In 14 cases with available survival data it was found that none of the clinicopathological parameters significantly correlated with survival (P>0.05). Methyl guanine DNA methyl transferase promoter methylation studies were performed using methylation-specific PCR in 16 cases which showed a methylation rate of 31.25% (5/16). The promoter methylation status did not correlate with the histological subtype and did not significantly affect survival (P>0.05). Although gliosarcomas continue to be treated in the same way as GBM, the role of chemotherapy with temozolomide is not clear. This cohort is the largest to date to uniformly receive the Stupp's protocol which is currently "standard of care" for GBM. A median overall survival of 18.5 months is substantially higher than previous studies, suggesting that temozolomide should be included in gliosarcoma therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Child
  • DNA / genetics
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Gliosarcoma / genetics*
  • Gliosarcoma / pathology
  • Gliosarcoma / surgery
  • Humans
  • Immunohistochemistry
  • Karnofsky Performance Status
  • Male
  • Methylation
  • Middle Aged
  • Neurosurgical Procedures
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Survival
  • Survival Analysis
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Tumor Suppressor Proteins
  • DNA
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes