Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

A.F. Leary, David Gonzalez de Castro, A.G. Nicholson, S. Ashley, A. Wotherspoon, M.E. O'Brien, S. Popat

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

INTRODUCTION: 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 (2.2 ng/μL), the mutation rate was 9.2%. CONCLUSION: 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.
Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalEuropean Journal of Cancer
Volume48
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Algorithms
  • Carcinoma, Non-Small-Cell Lung
  • DNA Mutational Analysis
  • Feasibility Studies
  • Female
  • Gene Frequency
  • Genes, erbB-1
  • Genetic Testing
  • Humans
  • Lung Neoplasms
  • Male
  • Mutation, Missense
  • Prognosis
  • Quality Control
  • Risk Factors
  • Specimen Handling

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