Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951.
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.
Mixed Research Unit, UMR 975, INSERM, National Institute of Health and Medical Research-Pierre and Marie Curie University, Pitie-Salpetriere Group Hospital, Paris, France.
Karima
K
Mokhtari
François
F
Ducray
Johan M
JM
Kros
Thierry
T
Gorlia
Ahmed
A
Idbaih
Martin
M
Taphoorn
Pieter
P
Wesseling
Khe
K
Hoang-Xuan
Martin
M
Van den Bent
Marc
M
Sanson
D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy; D011344:Procarbazine / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D017384:Sequence Deletion; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
D007381:Intermediate Filament Proteins; D025521:Tumor Suppressor Proteins; C046643:alpha-internexin; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes