title: 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 cell lung carcinoma [ERMETIC] project--part 1).
abstract: BACKGROUND
  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.
authors.affiliation: Laboratoire de Biologie Moléculaire, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Beau-Faller
authors.forename: Armelle
authors.initials: A
authors.lastname: Degeorges
authors.forename: Estelle
authors.initials: E
authors.lastname: Rolland
authors.forename: Mounia
authors.initials: M
authors.lastname: Mounawar
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.forename: Virginie
authors.initials: V
authors.lastname: Poulot
authors.forename: Audrey
authors.initials: A
authors.lastname: Mauguen
authors.forename: Véronique
authors.initials: V
authors.lastname: Barbu
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Hélène
authors.initials: H
authors.lastname: Blons
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Boyer
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Florence
authors.initials: F
authors.lastname: de Fraipont
authors.forename: Sarab
authors.initials: S
authors.lastname: Lizard
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Patrick
authors.initials: P
authors.lastname: Saulnier
authors.forename: Delphine
authors.initials: D
authors.lastname: Prunier-Mirebeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Richard
authors.forename: Claire
authors.initials: C
authors.lastname: Danel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005602:France; D006801:Humans; D007753:Laboratories; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016612:Paraffin Embedding; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015203:Reproducibility of Results; D016037:Single-Blind Method; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins