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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
- Source :
- PloS one, Vol. 12, No 6 (2017) P. e0178351, PLoS ONE, Vol 12, Iss 6, p e0178351 (2017), Andreiuolo, F, Le Teuff, G, Bayar, M A, Kilday, J P, Pietsch, T, von Bueren, A O, Witt, H, Korshunov, A, Modena, P, Pfister, S M, Pagès, M, Castel, D, Giangaspero, F, Chimelli, L, Varlet, P, Rutkowski, S, Frappaz, D, Massimino, M, Grundy, R & Grill, J 2017, ' Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication : A new model for risk stratification ', PLoS ONE, vol. 12, no. 6, e0178351 . https://doi.org/10.1371/journal.pone.0178351, PLoS ONE
- Publication Year :
- 2017
-
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.
- Subjects :
- DNA copy number variations
Oncology
Ependymoma
Male
medicine.medical_treatment
Cancer Treatment
lcsh:Medicine
Pediatrics
Biochemistry
survival analysis
Tenascin / metabolism
age of onset
0302 clinical medicine
Medicine and Health Sciences
Age of Onset
humans
lcsh:Science
Child
Neurological Tumors
child
human pair 1
Multidisciplinary
Manchester Cancer Research Centre
biology
Tenascin C
Hazard ratio
Tenascin
Multimodal therapy
Prognosis
child preschool
female
Neurology
Chromosomes, Human, Pair 1
030220 oncology & carcinogenesis
Child, Preschool
Cohort
Female
Research Article
Clinical Oncology
chromosomes
medicine.medical_specialty
ependymoma
DNA Copy Number Variations
Ependymoma / diagnosis
Radiation Therapy
Ependymoma / metabolism
Surgical and Invasive Medical Procedures
03 medical and health sciences
male
Diagnostic Medicine
chromosomes, human pair 1
infant
prognosis
Internal medicine
Cancer Detection and Diagnosis
medicine
Humans
Survival rate
Surgical Resection
business.industry
Proportional hazards model
ResearchInstitutes_Networks_Beacons/mcrc
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Infant
medicine.disease
Survival Analysis
Surgery
Radiation therapy
biology.protein
Ependymoma / genetics
lcsh:Q
Clinical Medicine
business
Chromosomes, Human, Pair 1 / genetics
Biomarkers
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PloS one, Vol. 12, No 6 (2017) P. e0178351, PLoS ONE, Vol 12, Iss 6, p e0178351 (2017), Andreiuolo, F, Le Teuff, G, Bayar, M A, Kilday, J P, Pietsch, T, von Bueren, A O, Witt, H, Korshunov, A, Modena, P, Pfister, S M, Pagès, M, Castel, D, Giangaspero, F, Chimelli, L, Varlet, P, Rutkowski, S, Frappaz, D, Massimino, M, Grundy, R & Grill, J 2017, ' Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication : A new model for risk stratification ', PLoS ONE, vol. 12, no. 6, e0178351 . https://doi.org/10.1371/journal.pone.0178351, PLoS ONE
- Accession number :
- edsair.doi.dedup.....3c232d8dbe7251dca2ef0c28ad1b5c30