Molecular analysis of peripheral non-squamous non-small cell lung cancer sampled by radial EBUS.
OBJECTIVE
Treatment optimization of non-squamous non-small-cell lung cancers (nonSq-NSCLC) relies on the molecular analysis of the tumour. We aimed to assess the predictive factors of molecular analysis feasibility (MAF) from samples of peripheral nonSq-NSCLC obtained by radial endobronchial ultrasound bronchoscopy (r-EBUS) and 1.5 mm microbiopsy forceps.


METHODS
We reviewed data from consecutive peripheral lung nodules sampled with r-EBUS between January 2012 and July 2014 at a single French University Hospital. nonSq-NSCLC were systematically analysed for EGFR, KRAS, ALK, HER2, PI3K and BRAF throughout the study, and c-MET and ROS1 alterations for the last 10 months.


RESULTS
Of 111 nonSq-NSCLC diagnosed by r-EBUS (113 procedures, mean nodule diameter 28 ± 15 mm), 88 were analysed for EGFR and ALK, 87 for KRAS, 86 for HER2, PI3K and BRAF and 14 for c-MET. Forty-one mutations were identified (23 KRAS, 10 EGFR, 2 BRAF, 1 HER2 and 5 ALK rearrangements). Four c-MET overexpressions were noted. MAF rose from 67% for the first 57 procedures to 89% for the last 56 procedures (P = 0.02) likely due to a higher number of biopsies performed (2 ± 1 vs 3 ± 2, P = 0.005). Upper or middle lobe location (OR 1.19, 95% CI: 1.02-1.38, P = 0.03), and at least three biopsies (OR 1.20, 95% CI: 1.04-1.40, P = 0.02) were predictive factors of MAF. Percentage of tumour cells, size of lesion and distance to the pleura did not correlate with MAF.


CONCLUSIONS
Multi-gene molecular analysis could be performed in nearly 80% of paraffin-embedded biopsies or smear specimens sampled by r-EBUS assisted bronchoscopy of peripheral tumoral lung nodules.
Clinique Pneumologique, Rouen University Hospital, Rouen, France.|CIC-INSERM 1404, Rouen University Hospital, Rouen, France.|EA 4108, LITIS QuantiF laboratory, University of Rouen, Rouen, France.
Florian
F
Guisier
Clinique Pneumologique, Rouen University Hospital, Rouen, France.|CIC-INSERM 1404, Rouen University Hospital, Rouen, France.|EA 4108, LITIS QuantiF laboratory, University of Rouen, Rouen, France.
Mathieu
M
Salaün
Clinique Pneumologique, Rouen University Hospital, Rouen, France.|CIC-INSERM 1404, Rouen University Hospital, Rouen, France.
Samy
S
Lachkar
Genetic Somatic Tumor Laboratory and Pathology Department, Rouen University Hospital, Rouen, France.
Aude
A
Lamy
Genetic Somatic Tumor Laboratory and Pathology Department, Rouen University Hospital, Rouen, France.
Nicolas
N
Piton
Clinique Pneumologique, Rouen University Hospital, Rouen, France.|CIC-INSERM 1404, Rouen University Hospital, Rouen, France.
Bérengère
B
Obstoy
Genetic Somatic Tumor Laboratory and Pathology Department, Rouen University Hospital, Rouen, France.|INSERM U1079, IRIB, Rouen University Hospital, Rouen, France.
Jean-Christophe
JC
Sabourin
Clinique Pneumologique, Rouen University Hospital, Rouen, France.|CIC-INSERM 1404, Rouen University Hospital, Rouen, France.|EA 4108, LITIS QuantiF laboratory, University of Rouen, Rouen, France.
Luc
L
Thiberville
D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001706:Biopsy; D001999:Bronchoscopy / Q000295:instrumentation / Q000379:methods*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018084:Ultrasonography, Interventional / Q000379:methods
D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C000626173:ALK protein, human; C062333:ROS1 protein, human; C482119:BRAF protein, human
lung adenocarcinoma; molecular analysis; navigational bronchoscopy; peripheral lung nodule; radial endobronchial-ultrasound bronchoscopy