Ki-67 and MCM6 labelling index are correlated with overall survival in anaplastic oligodendroglioma, IDH1-mutant and 1p/19q codeleted: a multicenter study from the French POLA Network

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Pouget, Celso | Hergalant, Sébastien | Lardenois, Emilie | Battaglia-Hsu, Shyue-Fang | Houlgatte, Rémi | Carpentier, C | Dehais, C. | Rech, Fabien | Taillandier, Luc | Colin, Carole | Figarella‑branger, Dominique | Gauchotte, Guillaume

Edité par CCSD -

International audience. Background & Objectives: Anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q codeleted (IDHmut+/1p19qcodel) are high grade gliomas. Only few prognostic markers were studied in this specific histomolecular subgroup. The primary aim of this study was to evaluate and compare the prognostic value of two proliferation markers, MCM6 and Ki-67, in a French multicenter series of IDHmut+/1p19qcodel AO (POLA network), using immunohistochemistry. Further transcriptomic approaches were implemented to uncover the molecular pathways associated with the overexpression of these markers.Methods: Two hundred and thirty-one IDHmut+/1p19qcodel AO cases were included from the French national POLA network. MCM6 and Ki-67 labelling index (LI) were evaluated using computer color image analyser. Transcriptomic data were analysed in a subset of 68 microarray samples from the French POLA Network.Results: High MCM6 (≥ 50%) and Ki-67 (≥ 15%) LI correlated with shorter overall survival (P=0.013 and P=0.004, respectively). A high proliferation index, defined by MCM6 ≥ 50% and/or Ki-67 ≥ 15%, was independently correlated to a shorter survival (P=0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki-67). Transcriptomic analyses revealed that while the high mRNA level of both MCM6 and Ki-67 were positively associated with clusters enriched in gene functions like cell cycle progression, DNA replication, mitosis, pro-neural phenotype as well as neurogenesis, they were negatively associated with clusters of other functions like microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta-amyloid binding, and postsynaptic specialization.Conclusion: In conclusion, both MCM6 and Ki-67 LI were correlated to overall survival. Because multivariate analyses showed that overexpression of MCM6 and/or Ki-67 was independently correlated to shorter survival, these two easy-to-use and costless markers could be used in association in daily practice in order to predict clinical outcome. Transcriptomics showed that IDHmut+/1p19qcodel AO are highly proliferative tumours with upregulated pro-neural phenotype associated genes, and downregulated immune response, glial differentiation, and myelin-related function.

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