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Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification

PURPOSE: Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. EXPERIMENTAL DESIGN: This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expre...

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Autores principales: Andreiuolo, Felipe, Le Teuff, Gwénaël, Bayar, Mohamed Amine, Kilday, John-Paul, Pietsch, Torsten, von Bueren, André O., Witt, Hendrik, Korshunov, Andrey, Modena, Piergiorgio, Pfister, Stefan M., Pagès, Mélanie, Castel, David, Giangaspero, Felice, Chimelli, Leila, Varlet, Pascale, Rutkowski, Stefan, Frappaz, Didier, Massimino, Maura, Grundy, Richard, Grill, Jacques
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472261/
https://www.ncbi.nlm.nih.gov/pubmed/28617804
http://dx.doi.org/10.1371/journal.pone.0178351
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author Andreiuolo, Felipe
Le Teuff, Gwénaël
Bayar, Mohamed Amine
Kilday, John-Paul
Pietsch, Torsten
von Bueren, André O.
Witt, Hendrik
Korshunov, Andrey
Modena, Piergiorgio
Pfister, Stefan M.
Pagès, Mélanie
Castel, David
Giangaspero, Felice
Chimelli, Leila
Varlet, Pascale
Rutkowski, Stefan
Frappaz, Didier
Massimino, Maura
Grundy, Richard
Grill, Jacques
author_facet Andreiuolo, Felipe
Le Teuff, Gwénaël
Bayar, Mohamed Amine
Kilday, John-Paul
Pietsch, Torsten
von Bueren, André O.
Witt, Hendrik
Korshunov, Andrey
Modena, Piergiorgio
Pfister, Stefan M.
Pagès, Mélanie
Castel, David
Giangaspero, Felice
Chimelli, Leila
Varlet, Pascale
Rutkowski, Stefan
Frappaz, Didier
Massimino, Maura
Grundy, Richard
Grill, Jacques
author_sort Andreiuolo, Felipe
collection PubMed
description PURPOSE: Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. EXPERIMENTAL DESIGN: This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. RESULTS: Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. CONCLUSION: Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.
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spelling pubmed-54722612017-07-03 Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification Andreiuolo, Felipe Le Teuff, Gwénaël Bayar, Mohamed Amine Kilday, John-Paul Pietsch, Torsten von Bueren, André O. Witt, Hendrik Korshunov, Andrey Modena, Piergiorgio Pfister, Stefan M. Pagès, Mélanie Castel, David Giangaspero, Felice Chimelli, Leila Varlet, Pascale Rutkowski, Stefan Frappaz, Didier Massimino, Maura Grundy, Richard Grill, Jacques PLoS One Research Article PURPOSE: Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. EXPERIMENTAL DESIGN: This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. RESULTS: Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. CONCLUSION: Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma. Public Library of Science 2017-06-15 /pmc/articles/PMC5472261/ /pubmed/28617804 http://dx.doi.org/10.1371/journal.pone.0178351 Text en © 2017 Andreiuolo et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Andreiuolo, Felipe
Le Teuff, Gwénaël
Bayar, Mohamed Amine
Kilday, John-Paul
Pietsch, Torsten
von Bueren, André O.
Witt, Hendrik
Korshunov, Andrey
Modena, Piergiorgio
Pfister, Stefan M.
Pagès, Mélanie
Castel, David
Giangaspero, Felice
Chimelli, Leila
Varlet, Pascale
Rutkowski, Stefan
Frappaz, Didier
Massimino, Maura
Grundy, Richard
Grill, Jacques
Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title_full Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title_fullStr Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title_full_unstemmed Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title_short Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification
title_sort integrating tenascin-c protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: a new model for risk stratification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472261/
https://www.ncbi.nlm.nih.gov/pubmed/28617804
http://dx.doi.org/10.1371/journal.pone.0178351
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