Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies

J Neurooncol. 2021 May;152(3):541-549. doi: 10.1007/s11060-021-03723-9. Epub 2021 Mar 4.

Abstract

Objective: To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab.

Method: We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates.

Results: No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone.

Conclusion: Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Keywords: Glioblastoma; MGMT promotor methylation; TP53 mutation; Temozolomide.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair Enzymes / genetics
  • Dacarbazine / therapeutic use
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Prognosis
  • Temozolomide / therapeutic use
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • O(6)-Methylguanine-DNA Methyltransferase
  • DNA Repair Enzymes
  • Temozolomide