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 th

Date publication

juin 2011

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BEAU-FALLER Michèle , Dr LIZARD Sarab , Pr PRETET Jean-Luc

Tous les auteurs :
Beau-Faller M, Degeorges A, Rolland E, Mounawar M, Antoine M, Poulot V, Mauguen A, Barbu V, Coulet F, Pretet JL, Bieche I, Blons H, Boyer JC, Buisine MP, de Fraipont F, Lizard S, Olschwang S, Saulnier P, Prunier-Mirebeau D, Richard N, Danel C, Brambilla E, Chouaid C, Zalcman G, Hainaut P, Michiels S, Cadranel J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/21532509

Résumé

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.

Référence

J Thorac Oncol. 2011 Jun;6(6):1006-15.