Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2017 Jun 15;12(6):e0178351.
doi: 10.1371/journal.pone.0178351. eCollection 2017.

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

Felipe Andreiuolo  1   2   3 , Gwénaël Le Teuff  4   5 , Mohamed Amine Bayar  4   5 , John-Paul Kilday  6   7 , Torsten Pietsch  8 , André O von Bueren  9   10 , Hendrik Witt  11 , Andrey Korshunov  12 , Piergiorgio Modena  13 , Stefan M Pfister  11 , Mélanie Pagès  2   14 , David Castel  1   15 , Felice Giangaspero  16   17 , Leila Chimelli  3 , Pascale Varlet  2   14 , Stefan Rutkowski  9 , Didier Frappaz  18 , Maura Massimino  19 , Richard Grundy  20 , Jacques Grill  1   15 ; SIOP Ependymoma Biology Working Group BIOMECA (BIOlogical Markers for Ependymomas in Children and Adolescents)
Affiliations
Multicenter Study

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

Felipe Andreiuolo et al. PLoS One. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan-Meier-based overall survival curves according to Tenascin-C (negative (43%), positive (57%)) (A) and 1q25 gain (negative (81%), positive (19%)) (B) (n = 470).
The hazard ratios (HR) and 95% confidence intervals, estimated through a univariate Cox model stratified by cohort, were for TNC: HRpos vs neg = 1.586 [1.105; 2.277] (p = 0.012) and for 1q25 gain: HRpos vs neg = 2.490 [1.721; 3.605] (p<0.0001).
Fig 2
Fig 2
A) Histogram of Pediatric Intracranial Ependymomas Score (PIES), B) Kaplan-Meier-based overall survival curves of 3 risk groups, C) Agreement between predicted and observed probability of death at 5 years and D) Kaplan-Meier-based overall survival curves of 3 risk groups using internal-external cross-validation approach.
Fig 3
Fig 3. Survival curves for posterior fossa tumor patients.
A) Global overall survival; B) Overall survival by cohort; C) by 1q status and D) by TNC expression.
Fig 4
Fig 4. Survival curves for supratentorial tumor patients.
A) Global overall survival; B) Overall survival by cohort; C) by 1q status and D) by TNC expression.
See this image and copyright information in PMC

References

    1. Andreiuolo F, Puget S, Peyre M, Dantas-Barbosa C, Boddaert N, Philippe C, et al. Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro-Oncol. 2010;12: 1126–1134. doi: 10.1093/neuonc/noq074 - DOI - PMC - PubMed
    1. Puget S, Grill J, Valent A, Bieche I, Dantas-Barbosa C, Kauffmann A, et al. Candidate genes on chromosome 9q33-34 involved in the progression of childhood ependymomas. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27: 1884–1892. doi: 10.1200/JCO.2007.15.4195 - DOI - PubMed
    1. Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, et al. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell. 2005;8: 323–335. doi: 10.1016/j.ccr.2005.09.001 - DOI - PubMed
    1. Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, et al. Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell. 2011;20: 143–157. doi: 10.1016/j.ccr.2011.07.007 - DOI - PMC - PubMed
    1. Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, et al. C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature. 2014;506: 451–455. doi: 10.1038/nature13109 - DOI - PMC - PubMed

Publication types

LinkOut - more resources