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Clinical Significance of Molecular Biomarkers in Glioblastoma

Published online by Cambridge University Press:  02 December 2014

C. Ang ,
M.-C. Guiot ,
A. V. Ramanakumar ,
D. Roberge  and
P. Kavan
C. Ang
Affiliation:
Department of Oncology, McGill University and the Segal Cancer Centre - Sir Mortimer B. Davis Jewish General Hospital
M.-C. Guiot
Affiliation:
Department of Pathology, McGill University Health Centre, Montreal Neurological Hospital
A. V. Ramanakumar
Affiliation:
Division of Cancer Epidemiology, Department of Oncology, McGill University
D. Roberge
Affiliation:
Department of Radiation Oncology, McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada
P. Kavan*
Affiliation:
Department of Oncology, McGill University and the Segal Cancer Centre - Sir Mortimer B. Davis Jewish General Hospital
*
3755 Rue Cote Ste Catherine, Pavillon E, Rm E-715 Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada.
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Abstract

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Aim:

To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM).

Materials & Methods:

Tissue specimens were analyzed for p53 mutations, EGFR amplification, loss of PTEN and p16, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Demographic and clinical data were gathered from medical records.

Results:

Clinical and pathological data of 125 patients were collected and analysed. MGMT promoter methylation was associated with improved median overall survival (OS) (61 vs. 42 weeks, p = 0.01) and was an important prognosticator independent of age at diagnosis, extent of resection and post-operative ECOG performance status (HR 2.04, 95% CI 1.11-3.75). Among patients with MGMT promoter methylation, survival was significantly improved with chemoradiotherapy (CRT) over radiotherapy (RT) alone (71 vs. 14 weeks, p < 0.01). Furthermore, amongst those treated with temozolomide (TMZ) based CRT, the presence of EGFR amplification, maintenance of PTEN and wild-type p53 and p16 were each associated with trends towards improved survival.

Conclusion:

MGMT promoter methylation is a strong, independent prognostic factor for OS in GBM. EGFR amplification, maintenance of PTEN, wild-type p53 and p16 all appear to be associated with improved survival in patients treated with CRT. However, the prognostic value of these biomarkers could not be ascertained and larger prospective studies are warranted.

Résumé:

RÉSUMÉ:Objectif:

Le but de l’etude etait de reviser l’impact des biomarqueurs moleculaires sur la reponse au traitement et la survie chez les patients atteints de glioblastome primaire (GBP).

Méthode:

Des echantillons de tissus ont ete analyses pour determiner la presence de mutations du gene p53, d’amplification du gene de EGFR, de perte de PTEN et de p16 et de methylation du promoteur de MGMT. Les donnees demographiques et cliniques ont ete tirees des dossiers cliniques.

Résultats:

Les donnees cliniques et anatomopathologiques de 125 patients ont ete recueillies et analysees. La methylation du promoteur de MGMT etait associee a une survie globale (SG) mediane amelioree, soit de 61 semaines par rapport a 42 semaines, (p = 0,01) et etait un facteur de pronostic important, independant de l’age au moment du diagnostic, de l’etendue de la resection et de l’indice de performance postoperatoire ECOG (RR 2,04 ; IC a 95% 1,11 a 3,75). Parmi les patients qui avaient une methylation du promoteur de MGMT, la survie etait amelioree significativement avec la chimioradiotherapie (CRT) par rapport a la radiotherapie seule, soit 71 semaines par rapport a 14 semaines (p < 0,01). De plus, parmi ceux qui avaient ete traites par la CRT a base de temozolomide, la presence d’amplification de EGFR, la conservation de PTEN et de p53 et p16 de type sauvage etaient chacune associees a une tendance a une survie amelioree.

Conclusion:

La methylation du promoteur de MGMT est un facteur de pronostic independent important pour la SG dans le GBM. L’amplification de EGFR, la conservation de PTEN, la presence de p53 et p16 de type sauvage semblent toutes associees a une meilleure survie chez les patients traites par la CRT. Cependant, la valeur de ces biomarqueurs n’a pu etre determinee et devra faire l’objet d’etudes prospectives plus considerables.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 5 , September 2010 , pp. 625 - 630
Copyright
Copyright © The Canadian Journal of Neurological 2010

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