Dataset Information

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

ABSTRACT:

Background

The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs).

Methods

The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing.

Results

1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023).

Conclusions

The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.

SUBMITTER: Figarella-Branger D

PROVIDER: S-EPMC4136899 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

Figarella-Branger Dominique D Mokhtari Karima K Dehais Caroline C Jouvet Anne A Uro-Coste Emmanuelle E Colin Carole C Carpentier Catherine C Forest Fabien F Maurage Claude-Alain CA Vignaud Jean-Michel JM Polivka Marc M Lechapt-Zalcman Emmanuelle E Eimer Sandrine S Viennet Gabriel G Quintin-Roué Isabelle I Aubriot-Lorton Marie-Hélène MH Diebold Marie-Danièle MD Loussouarn Delphine D Lacroix Catherine C Rigau Valérie V Laquerrière Annie A Vandenbos Fanny F Michalak Sophie S Sevestre Henri H Peoch Michel M Labrousse François F Christov Christo C Kemeny Jean-Louis JL Chenard Marie-Pierre MP Chiforeanu Danchristian D Ducray François F Idbaih Ahmed A

Neuro-oncology 20140409 9

<h4>Background</h4>The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs).<h4>Methods</h4>The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing.<h4>Results</h4>1p/19q codeletion was present in 79% of cases and was a ...[more]

PMID: 24723566

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Project description:Approximately 50-80% of oligodendrogliomas demonstrate a combined loss of chromosome 1p and 19q. Chromosome 1p/19q deletion, appearing early in tumorigenesis, is associated with improved clinical outcomes, including response to chemotherapy and radiation. Although many hypotheses have been proposed, the molecular mechanisms underlying improved clinical outcomes with 1p/19q deletion in oligodendrogliomas have not been characterized fully. To investigate the molecular differences between oligodendrogliomas, we employed an unbiased proteomic approach using microcapillary liquid chromatography mass spectrometry, along with a quantitative technique called isotope-coded affinity tags, on patient samples of grade II oligodendrogliomas. Following conventional biochemical separation of pooled tumor tissue from five samples of undeleted and 1p/19q deleted grade II oligodendrogliomas into nuclei-, mitochondria-, and cytosol-enriched fractions, relative changes in protein abundance were quantified. Among the 442 total proteins identified, 163 nonredundant proteins displayed significant changes in relative abundance in at least one of the three fractions between oligodendroglioma with and without 1p/19q deletion. Bioinformatic analyses of differentially regulated proteins supported the potential importance of metabolism and invasion/migration to the codeleted phenotype. A subset of altered proteins, including the pro-invasive extracellular matrix protein BCAN, was further validated by Western blotting as candidate markers for the more aggressive undeleted phenotype. These studies demonstrate the utility of proteomic analysis to identify candidate biological motifs and molecular mechanisms that drive differential malignancy related to 1p19q phenotypes. Future analysis of larger patient samples are warranted to further refine biomarker panels to predict biological behavior and assist in the identification of deleted gene products that define the 1p/19q phenotype.

Dataset Information

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

Background

Methods

Results

Conclusions

Publications

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

Similar Datasets

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