Clinical validation of the CE-IVD marked Therascreen MGMT kit in a cohort of glioblastoma patients

Article type: Research Article

Authors: Quillien, Véronique^{a; b; *} | Lavenu, Audrey^{c; d} | Ducray, François^{e; f} | Meyronet, David^{e; f} | Chinot, Olivier^g | Fina, Frédéric^h | Sanson, Marcⁱ | Carpentier, Catherineⁱ | Karayan-Tapon, Lucie^{j; k} | Rivet, Pierre^k | Entz-Werle, Natacha^{l; m} | Legrain, Michèle^l | Zalcman, Emmanuèle Lechaptⁿ | Levallet, Guenaelleⁿ | Escande, Fabienne^o | Ramirez, Carole^o | Chiforeanu, Dan^p | Vauleon, Elodie^{a; b} | Figarella-Branger, Dominique^{g; q}

Affiliations: [a] Centre Eugène Marquis, Rennes, France | [b] INSERM U1242, Université de Rennes 1, Rennes, France | [c] Faculté de Médecine, Université Rennes 1, Rennes, France | [d] INSERM CIC 0203, Université de Rennes 1, Rennes, France | [e] Hospices Civils de Lyon, Lyon, France | [f] Université de Lyon1, Villeurbanne, France | [g] CHU Timone, Marseille, France | [h] Faculté de Médecine Secteur Nord, Marseille, France | [i] INSERM CNRS, Sorbonne Universités UPMC Université Paris 06, Paris, France | [j] INSERM U1084, Université de Poitiers, Poitiers, France | [k] CHU de Poitiers, Poitiers, France | [l] CHRU Hautepierre, Strasbourg, France | [m] EA 3430, Progression Tumorale et Microenvironnement, Approches Translationnelles et Épidémiologie, Université de Strasbourg, Strasbourg, France | [n] CHU Caen, Département de Pathologie, Caen, France | [o] CHRU de Lille, Lille, France | [p] CHU de Rennes, Rennes, France | [q] INSERM U911 CRO2, Université de la Méditerranée, Marseille, France

Correspondence: [*] Corresponding author: Véronique Quillien, Centre Eugène Marquis, F-35042 Rennes, France. Tel.: +33 299 253 190; Fax: +33 299 253 164; E-mail: [email protected].

Abstract: BACKGROUND: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76–79. METHODS: We performed a comparison of these two assays to evaluate the potential impact of this shift in analyzed CpGs. Therascreen analysis was centrally performed for 102 glioblastoma patients, who were part of a prospective multicenter trial. RESULTS: A strong correlation was observed for the mean values of the 4 or 5 analyzed CpGs, with lower values recorded using the Therascreen assay, especially for values greater than 20%. When considering a classification in 3 categories (> 12%: methylated; ⩽ 8%: unmethylated; 9–12%: grey zone), 93% of patients were identically classified between the two assays. Using a binary classification, 95% and 97% of patients were identically classified with cut-offs of 8% and 12%, respectively. A strong prognostic significance was observed for both assays: median overall survival were 15.9 months and 34.9 months for respectively unmethylated and methylated patients with either test. CONCLUSION: The results demonstrate that these assays may be used interchangeably.

Keywords: Glioblastoma, MGMT methylation, pyrosequencing, CE-IVD kit

DOI: 10.3233/CBM-170191

Journal: Cancer Biomarkers, vol. 20, no. 4, pp. 435-441, 2017