title: EGFR gene copy number alterations are not a useful screening tool for predicting EGFR mutation status in lung adenocarcinoma.
abstract: We investigated if gene copy number (GCN) alterations of the epidermal growth factor receptor (EGFR), as detected by silver enhanced in situ hybridisation (SISH), could be used to select patients for EGFR mutation testing. Resected lung adenocarcinoma specimens with adequate tumour were identified. EGFR SISH was performed using the Ventana Benchmark Ultra platform. EGFR GCN was classified according to the Colorado Classification System. EGFR mutations were scanned by high resolution melting and confirmed by Sanger sequencing. Thirty-four of 96 tumours were EGFR SISH positive (35%), and 31 of 96 tumours harboured one or more EGFR mutations (32%). Of 31 EGFR-mutant tumours, 18 were EGFR SISH positive (58%). There was a statistically significant relationship between the presence of an EGFR mutation and EGFR GCN (p = 0.003). Thirteen of 31 EGFR-mutant tumours were EGFR SISH negative (42%), and 16 of 65 EGFR-wild type tumours were EGFR SISH positive (24%). The sensitivity, specificity, positive predictive value and negative predictive value were 58%, 75%, 52.9% and 79%, respectively. Despite a significant relationship between EGFR GCN alterations and EGFR mutations, our results indicate that EGFR GCN as detected by SISH is not a suitable way to select patients for EGFR mutation testing.
authors.affiliation: 1Department of Anatomical Pathology, St Vincent's Hospital, University of Melbourne, Fitzroy 2Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne 3Department of Medical Oncology, St Vincent's Hospital, University of Melbourne, Fitzroy 4University of Melbourne Department of Surgery, St Vincent's Hospital, Fitzroy 5Department of Respiratory and Sleep Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Russell
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Hongdo
authors.initials: H
authors.lastname: Do
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Clay
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Moore
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Wright
authors.forename: Matthew
authors.initials: M
authors.lastname: Conron
authors.forename: Zoe
authors.initials: Z
authors.lastname: Wainer
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
authors.forename: Sue-Anne
authors.initials: SA
authors.lastname: McLachlan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors