INI1 immunohistochemical expression in glioblastoma: correlation with MGMT gene promoter methylation status and patient survival

Pathology. 2011 Jan;43(1):17-23. doi: 10.1097/PAT.0b013e328340bb26.

Abstract

Aims: INI1 expression and its correlation with MGMT gene promoter methylation status and follow-up was investigated in 77 surgically removed glioblastomas then treated with radiotherapy (RT) or RT plus temozolomide (TMZ).

Methods: INI1 was determined by immunohistochemistry and MGMT by methylation-specific PCR.

Results: INI1 was expressed in 83.1% of cases. The median overall survival (OS) was 13.6 months in INI1+ tumours and 7.2 months in INI1- tumours. 31.3% of patients with INI1+ tumours were alive compared with 15.4% of patients with INI1- tumours. MGMT methylation was detected in 31.2% of cases. OS was significantly different between patients with methylated tumours and un-methylated tumours (p < 0.04), and between patients with RT+ TMZ and RT alone (p < 0.001). Considering both treatment and MGMT, the difference in OS was significant (p < 0.002). The difference in OS according to MGMT and INI1 was significant (p < 0.04). The longest median OS was recorded among methylated and INI1+ tumours. Among un-methylated tumours, the median OS was 11.1 months in INI1+ and 6.5 months in INI1- tumours. No patients were alive with un-methylated and INI1- tumours.

Conclusions: Loss of INI1 immunohistochemical expression in glioblastoma may be indicating an underlying molecular aberration accounting for the more aggressive clinical behaviour.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioblastoma* / mortality
  • Glioblastoma* / pathology
  • Humans
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics*
  • SMARCB1 Protein
  • Supratentorial Neoplasms* / genetics
  • Supratentorial Neoplasms* / metabolism
  • Supratentorial Neoplasms* / mortality
  • Supratentorial Neoplasms* / pathology
  • Survival Rate
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes