Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy

Karima Mokhtari, François Ducray, Johan M. Kros, Thierry Gorlia, Ahmed Idbaih, Martin J B Taphoorn, Pieter Wesseling, Khe Hoang-Xuan, Martin J van den Bent, Marc Sanson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Although it has been demonstrated that the neuronal intermediate filament alpha-internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs). METHODS: INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression-free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH1/IDH2) mutation, and O-6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status. RESULTS: INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV. CONCLUSIONS: In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy.

Original languageEnglish
Pages (from-to)3014-3026
Number of pages13
JournalCancer
Volume117
Issue number13
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

Keywords

  • 19q deletion
  • 1p deletion
  • alpha-internexin
  • clinical trial
  • glioma
  • oligodendroglioma
  • procarbazine, lomustine, and vincristine
  • prognostic marker
  • proneural
  • radiotherapy

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