Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.
BACKGROUND
EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome.


METHODS
Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2.


RESULTS
In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/μL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/μL), the mutation rate was 9.2%.


CONCLUSIONS
Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation.
Department of Medical Oncology, Royal Marsden Hospital, London, UK.
Alexandra F
AF
Leary
David Gonzalez de
DG
Castro
Andrew G
AG
Nicholson
Sue
S
Ashley
Andrew
A
Wotherspoon
Mary E R
ME
O'Brien
Sanjay
S
Popat
D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods / Q000706:statistics & numerical data; D005240:Feasibility Studies; D005260:Female; D005787:Gene Frequency; D018773:Genes, erbB-1; D005820:Genetic Testing / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D011379:Prognosis; D011786:Quality Control; D012307:Risk Factors; D013048:Specimen Handling