Cross-Validation Study for Epidermal Growth Factor Receptor and KRAS Mutation Detection in 74 Blinded Non-small Cell Lung Carcinoma Samples: A Total of 5550 Exons Sequenced by 15 Molecular French Laboratories (Evaluation of the EGFR Mutation Status for the Administration of EGFR-TKIs in Non-Small Lung Carcinoma [ERMETIC] Project-Part 1).

Michèle Beau-Faller (1) , Armelle Degeorges (2) , Estelle Rolland (3) , Mounia Mounawar (4) , Martine Antoine (5) , Virginie Poulot (6) , Audrey Mauguen (3) , Véronique Barbu (7) , Florence Coulet (7) , Jean-Luc Prétet (8, 9) , Ivan Bièche (10) , Hélène Blons (11) , Jean-Christophe Boyer (12) , Marie-Pierre Buisine (13) , Florence de Fraipont (14) , Sarab Lizard (15) , Sylviane Olschwang (16) , Patrick Saulnier (17) , Delphine Prunier-Mirebeau , Nicolas Richard (18) , Claire Danel (19) , Elisabeth Brambilla (20) , Christos Chouaid (21, 6) , Gérard Zalcman (22) , Pierre Hainaut (23) , Stefan Michiels (24) , Jacques Cadranel

1 Laboratoire de Biochimie et de Biologie Moléculaire
2 Unité de pharmacologie
3 IGR - Institut Gustave Roussy
4 Unit of Environment Cancer Epidemiology
5 CHU Tenon [AP-HP]
6 CHU Saint-Antoine [AP-HP]
7 PMT EA 4438 - Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire [UNIV Strasbourg]
8 CEF2P / CARCINO - Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181)
9 Laboratoire de biologie cellulaire et moléculaire (CHRU Besançon)
10 Genetique Moleculaire des Cancers d'Origine Epitheliale
11 U775 (IFR95) - Bases moléculaires de la réponse aux xénobiotiques
12 Laboratoire de Biochimie [CHRU Nîmes]
13 Institut de Biochimie et Biologie Moléculaire [CHRU Lille]
14 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
15 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
16 CRCM / U891 Inserm - Centre de Recherche en Cancérologie de Marseille
17 Ingénierie de la vectorisation particulaire
18 Service de Génétique [CHU Caen]
19 Service d'anatomo-pathologie [CHU HEGP]
20 Département d'anatomie et cythologie pathologique
21 ESIM - Epidémiologie des maladies infectieuses et modélisation
22 Service de Pneumologie
23 IACR - International Agency for Cancer Research
24 SBE - Service de biostatistique et d'épidémiologie

INTRODUCTION:: The Evaluation of the epidermal growth factor receptor (EGFR) Mutation status for the administration of EGFR-Tyrosine Kinase Inhibitors in non-small cell lung Carcinoma (NSCLC) (ERMETIC) project part 1 assessed the accuracy of EGFR and KRAS mutations detection in NSCLC among 15 French centers. METHODS:: The 15 ERMETIC centers selected 74 NSCLC surgical specimens from previously untreated patients. Paraffin and paired frozen DNA were sequenced for EGFR exons 18 to 21 and KRAS exon 2 by an external molecular laboratory, yielding a gold standard. The 74 blinded paraffin DNAs were redistributed to the 15 ERMETIC laboratories for sequencing of a total of 5550 exons. Results were compared with the gold standard and between centers by discordance rates and kappa statistics. RESULTS:: The gold standard included 39 mutated samples with 22 EGFR and 17 KRAS mutated samples. Kappa statistics showed that 10, 6, and 6 of the 15 ERMETIC centers had a moderate to good kappa score, when compared with external laboratory for EGFR exon 19, EGFR exon 21, and KRAS exon 2, respectively. Kappa statistics showed moderate score between centers which increased to good for EGFR exon 19 mutation when removing 16 poor-quality samples with high nonamplificable rates. CONCLUSIONS:: Paraffin-embedded specimens may represent a suitable source of DNA for sequencing analyses in ERMETIC centers. EGFR exon 19 deletions were most accurately detected by ERMETIC centers. Ease and accuracy of results, depended more on the quality of sample than on the difference in molecular sequencing procedures between centers, emphasize the need of preanalytical quality control programs.

Domaines: Cancer

Michèle Beau-Faller, Armelle Degeorges, Estelle Rolland, Mounia Mounawar, Martine Antoine, et al.. Cross-Validation Study for Epidermal Growth Factor Receptor and KRAS Mutation Detection in 74 Blinded Non-small Cell Lung Carcinoma Samples: A Total of 5550 Exons Sequenced by 15 Molecular French Laboratories (Evaluation of the EGFR Mutation Status for the Administration of EGFR-TKIs in Non-Small Lung Carcinoma [ERMETIC] Project-Part 1).. Journal of Thoracic Oncology, 2011, 6, pp.1006-1015. ⟨10.1097/JTO.0b013e318211dcee⟩. ⟨hal-00593534⟩