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

Dominique Figarella-Branger; Karima Mokhtari; Caroline Dehais; Anne Jouvet; Emmanuelle Uro-Coste; Carole Colin; Catherine Carpentier; Fabien Forest; Claude Alain Maurage; Jean Michel Vignaud; Marc Polivka; Emmanuelle Lechapt-Zalcman; Sandrine Eimer; Gabriel Viennet; Isabelle Quintin-Roué; Marie Hélène Aubriot-Lorton; Marie Danièle Diebold; Delphine Loussouarn; Catherine Lacroix; Valérie Rigau; Annie Laquerrière; Fanny Vandenbos; Sophie Michalak; Henri Sevestre; Michel Peoch; François Labrousse; Christo Christov; Jean Louis Kemeny; Marie Pierre Chenard; Danchristian Chiforeanu; François Ducray; Ahmed Idbaih; Christine Desenclos; Philippe Menei; Edmond Al Nader; Joel Godard; Stéphanie Servagi-Vernat; Antoine Carpentier; Hugues Loiseau; Phong Dam-Hieu; Jean Sebastien Guillamo; Evelyne Emery; Pierre Verelle; Xavier Durando; Thierry Faillot; Caroline Le Guerinel; François Ghiringhelli; Fabrice Parker; Clovis Adam; François Dubois; Carole Ramirez; Edouard Marcel Gueye; Jerome Honnorat; Olivier Chinot; Luc Bauchet; Patrick Beauchesne; Mario Campone; Jean Sébastien Frenel; Denys Fontaine; Chantal Campello; Pascal Roger; Anne Heitzmann; Mélanie Fesneau; Jean Yves Delattre; Selma Elouadhani-Hamdi; Damien Ricard; Philippe Colin; Elodie Vauléon; Olivier Langlois; Marie Janette Motsuo Fotso; Marie Andraud; Servane Mouton; Georges Noel; Nicolas Desse; Raoulin Soulard; Elisabeth Cohen-Moyal; Vincent Lubrano; Frederic Dhermain

doi:10.1093/neuonc/nou047

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

Dominique Figarella-Branger, Karima Mokhtari, Caroline Dehais, Anne Jouvet, Emmanuelle Uro-Coste, Carole Colin, Catherine Carpentier, Fabien Forest, Claude Alain Maurage, Jean Michel Vignaud, Marc Polivka, Emmanuelle Lechapt-Zalcman, Sandrine Eimer, Gabriel Viennet, Isabelle Quintin-Roué, Marie Hélène Aubriot-Lorton, Marie Danièle Diebold, Delphine Loussouarn, Catherine Lacroix, Valérie RigauAnnie Laquerrière, Fanny Vandenbos, Sophie Michalak, Henri Sevestre, Michel Peoch, François Labrousse, Christo Christov, Jean Louis Kemeny, Marie Pierre Chenard, Danchristian Chiforeanu, François Ducray, Ahmed Idbaih, Christine Desenclos, Philippe Menei, Edmond Al Nader, Joel Godard, Stéphanie Servagi-Vernat, Antoine Carpentier, Hugues Loiseau, Phong Dam-Hieu, Jean Sebastien Guillamo, Evelyne Emery, Pierre Verelle, Xavier Durando, Thierry Faillot, Caroline Le Guerinel, François Ghiringhelli, Fabrice Parker, Clovis Adam, François Dubois, Carole Ramirez, Edouard Marcel Gueye, Jerome Honnorat, Olivier Chinot, Luc Bauchet, Patrick Beauchesne, Mario Campone, Jean Sébastien Frenel, Denys Fontaine, Chantal Campello, Pascal Roger, Anne Heitzmann, Mélanie Fesneau, Jean Yves Delattre, Selma Elouadhani-Hamdi, Damien Ricard, Philippe Colin, Elodie Vauléon, Olivier Langlois, Marie Janette Motsuo Fotso, Marie Andraud, Servane Mouton, Georges Noel, Nicolas Desse, Raoulin Soulard, Elisabeth Cohen-Moyal, Vincent Lubrano, Frederic Dhermain

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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.

Original language	English
Pages (from-to)	1244-1254
Number of pages	11
Journal	Neuro-Oncology
Volume	16
Issue number	9
DOIs	https://doi.org/10.1093/neuonc/nou047
Publication status	Published - 1 Jan 2014

Keywords

1p/19q codeletion
Anaplastic oligodendrogliomas
Microvascular proliferation
Mitoses
Necrosis

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10.1093/neuonc/nou047

Cite this

Figarella-Branger, D., Mokhtari, K., Dehais, C., Jouvet, A., Uro-Coste, E., Colin, C., Carpentier, C., Forest, F., Maurage, C. A., Vignaud, J. M., Polivka, M., Lechapt-Zalcman, E., Eimer, S., Viennet, G., Quintin-Roué, I., Aubriot-Lorton, M. H., Diebold, M. D., Loussouarn, D., Lacroix, C., ... Dhermain, F. (2014). Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations. Neuro-Oncology, 16(9), 1244-1254. https://doi.org/10.1093/neuonc/nou047

@article{e840dbbeab384e70b863a315567f0088,

title = "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.",

keywords = "1p/19q codeletion, Anaplastic oligodendrogliomas, Microvascular proliferation, Mitoses, Necrosis",

author = "Dominique Figarella-Branger and Karima Mokhtari and Caroline Dehais and Anne Jouvet and Emmanuelle Uro-Coste and Carole Colin and Catherine Carpentier and Fabien Forest and Maurage, {Claude Alain} and Vignaud, {Jean Michel} and Marc Polivka and Emmanuelle Lechapt-Zalcman and Sandrine Eimer and Gabriel Viennet and Isabelle Quintin-Rou{\'e} and Aubriot-Lorton, {Marie H{\'e}l{\`e}ne} and Diebold, {Marie Dani{\`e}le} and Delphine Loussouarn and Catherine Lacroix and Val{\'e}rie Rigau and Annie Laquerri{\`e}re and Fanny Vandenbos and Sophie Michalak and Henri Sevestre and Michel Peoch and Fran{\c c}ois Labrousse and Christo Christov and Kemeny, {Jean Louis} and Chenard, {Marie Pierre} and Danchristian Chiforeanu and Fran{\c c}ois Ducray and Ahmed Idbaih and Christine Desenclos and Philippe Menei and {Al Nader}, Edmond and Joel Godard and St{\'e}phanie Servagi-Vernat and Antoine Carpentier and Hugues Loiseau and Phong Dam-Hieu and Guillamo, {Jean Sebastien} and Evelyne Emery and Pierre Verelle and Xavier Durando and Thierry Faillot and {Le Guerinel}, Caroline and Fran{\c c}ois Ghiringhelli and Fabrice Parker and Clovis Adam and Fran{\c c}ois Dubois and Carole Ramirez and Gueye, {Edouard Marcel} and Jerome Honnorat and Olivier Chinot and Luc Bauchet and Patrick Beauchesne and Mario Campone and Frenel, {Jean S{\'e}bastien} and Denys Fontaine and Chantal Campello and Pascal Roger and Anne Heitzmann and M{\'e}lanie Fesneau and Delattre, {Jean Yves} and Selma Elouadhani-Hamdi and Damien Ricard and Philippe Colin and Elodie Vaul{\'e}on and Olivier Langlois and Fotso, {Marie Janette Motsuo} and Marie Andraud and Servane Mouton and Georges Noel and Nicolas Desse and Raoulin Soulard and Elisabeth Cohen-Moyal and Vincent Lubrano and Frederic Dhermain",

year = "2014",

month = jan,

day = "1",

doi = "10.1093/neuonc/nou047",

language = "English",

volume = "16",

pages = "1244--1254",

journal = "Neuro-Oncology",

issn = "1522-8517",

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Figarella-Branger, D, Mokhtari, K, Dehais, C, Jouvet, A, Uro-Coste, E, Colin, C, Carpentier, C, Forest, F, Maurage, CA, Vignaud, JM, Polivka, M, Lechapt-Zalcman, E, Eimer, S, Viennet, G, Quintin-Roué, I, Aubriot-Lorton, MH, Diebold, MD, Loussouarn, D, Lacroix, C, Rigau, V, Laquerrière, A, Vandenbos, F, Michalak, S, Sevestre, H, Peoch, M, Labrousse, F, Christov, C, Kemeny, JL, Chenard, MP, Chiforeanu, D, Ducray, F, Idbaih, A, Desenclos, C, Menei, P, Al Nader, E, Godard, J, Servagi-Vernat, S, Carpentier, A, Loiseau, H, Dam-Hieu, P, Guillamo, JS, Emery, E, Verelle, P, Durando, X, Faillot, T, Le Guerinel, C, Ghiringhelli, F, Parker, F, Adam, C, Dubois, F, Ramirez, C, Gueye, EM, Honnorat, J, Chinot, O, Bauchet, L, Beauchesne, P, Campone, M, Frenel, JS, Fontaine, D, Campello, C, Roger, P, Heitzmann, A, Fesneau, M, Delattre, JY, Elouadhani-Hamdi, S, Ricard, D, Colin, P, Vauléon, E, Langlois, O, Fotso, MJM, Andraud, M, Mouton, S, Noel, G, Desse, N, Soulard, R, Cohen-Moyal, E, Lubrano, V & Dhermain, F 2014, 'Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations', Neuro-Oncology, vol. 16, no. 9, pp. 1244-1254. https://doi.org/10.1093/neuonc/nou047

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations. / Figarella-Branger, Dominique; Mokhtari, Karima; Dehais, Caroline et al.
In: Neuro-Oncology, Vol. 16, No. 9, 01.01.2014, p. 1244-1254.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

AU - Figarella-Branger, Dominique

AU - Mokhtari, Karima

AU - Dehais, Caroline

AU - Jouvet, Anne

AU - Uro-Coste, Emmanuelle

AU - Colin, Carole

AU - Carpentier, Catherine

AU - Forest, Fabien

AU - Maurage, Claude Alain

AU - Vignaud, Jean Michel

AU - Polivka, Marc

AU - Lechapt-Zalcman, Emmanuelle

AU - Eimer, Sandrine

AU - Viennet, Gabriel

AU - Quintin-Roué, Isabelle

AU - Aubriot-Lorton, Marie Hélène

AU - Diebold, Marie Danièle

AU - Loussouarn, Delphine

AU - Lacroix, Catherine

AU - Rigau, Valérie

AU - Laquerrière, Annie

AU - Vandenbos, Fanny

AU - Michalak, Sophie

AU - Sevestre, Henri

AU - Peoch, Michel

AU - Labrousse, François

AU - Christov, Christo

AU - Kemeny, Jean Louis

AU - Chenard, Marie Pierre

AU - Chiforeanu, Danchristian

AU - Ducray, François

AU - Idbaih, Ahmed

AU - Desenclos, Christine

AU - Menei, Philippe

AU - Al Nader, Edmond

AU - Godard, Joel

AU - Servagi-Vernat, Stéphanie

AU - Carpentier, Antoine

AU - Loiseau, Hugues

AU - Dam-Hieu, Phong

AU - Guillamo, Jean Sebastien

AU - Emery, Evelyne

AU - Verelle, Pierre

AU - Durando, Xavier

AU - Faillot, Thierry

AU - Le Guerinel, Caroline

AU - Ghiringhelli, François

AU - Parker, Fabrice

AU - Adam, Clovis

AU - Dubois, François

AU - Ramirez, Carole

AU - Gueye, Edouard Marcel

AU - Honnorat, Jerome

AU - Chinot, Olivier

AU - Bauchet, Luc

AU - Beauchesne, Patrick

AU - Campone, Mario

AU - Frenel, Jean Sébastien

AU - Fontaine, Denys

AU - Campello, Chantal

AU - Roger, Pascal

AU - Heitzmann, Anne

AU - Fesneau, Mélanie

AU - Delattre, Jean Yves

AU - Elouadhani-Hamdi, Selma

AU - Ricard, Damien

AU - Colin, Philippe

AU - Vauléon, Elodie

AU - Langlois, Olivier

AU - Fotso, Marie Janette Motsuo

AU - Andraud, Marie

AU - Mouton, Servane

AU - Noel, Georges

AU - Desse, Nicolas

AU - Soulard, Raoulin

AU - Cohen-Moyal, Elisabeth

AU - Lubrano, Vincent

AU - Dhermain, Frederic

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - 1p/19q codeletion

KW - Anaplastic oligodendrogliomas

KW - Microvascular proliferation

KW - Mitoses

KW - Necrosis

UR - http://www.scopus.com/inward/record.url?scp=84903394685&partnerID=8YFLogxK

U2 - 10.1093/neuonc/nou047

DO - 10.1093/neuonc/nou047

M3 - Article

C2 - 24723566

AN - SCOPUS:84903394685

SN - 1522-8517

VL - 16

SP - 1244

EP - 1254

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - 9

ER -

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

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