External Quality Assurance Results Reveal EGFR Test Errors

External quality assurance is crucial for laboratories conducting epidermal growth factor receptor mutation testing for lung cancer patients

medwireNews: A significant proportion of Epidermal growth factor receptor (EGFR) tests for non-small-cell lung cancer (NSCLC) Mutations are inaccurate, suggest findings from a pilot external quality assurance (EQA) study.

The most common errors were false-negative and false-positive results, both of which may lead to detrimental treatment decisions that could be “extremely harmful for NSCLC patients”, caution Simon Patton, from St Mary’s Hospital in Manchester, UK, and co-workers.

The research was initiated by the European Thoracic Oncology Platform and the European Molecular Genetics Quality Network, as well as leading organisations involved in NSCLC testing including the European Society for Medical Oncology and the European Society of Pathology.

The samples sent to laboratories were homogenous mixtures of mutant and Wild-type cell lines processed to mimic NSCLC biopsy samples as closely as possible, the authors explain in the British Journal of Cancer.

For an initial proof-of-principle round of the study, 25 laboratories from 13 countries processed 10 samples, most commonly using Polymerase chain reaction (PCR)/sequencing (34%) or real-time PCR (34%). Two false–negative results were reported and sample swaps led to 24 Genotype errors.

In the second round of the study, 91 of the 117 registered laboratories in 30 countries submitted results, with PCR/sequencing (39%) and/or real-time PCR (18.6%) again being the most common techniques used.

Genotype errors were reported in 8.1% of samples, the majority (82.4%) of which were false–negative tests. Other types of error included analytical test failure (3.4%), genotype mispositioning (0.8%) and mutation nomenclature mistakes (3.9%).

Overall, 46 laboratories passed the second round of testing. The 18 laboratories that were classed as poor performers and did not pass the EQA were invited to participate in a third round of the study, 17 of which returned results.

Genotyping errors were reported for 10.6% of samples, 94.4% of which were false–negative errors, and 1.8% had analytical test failures. Of concern, eight laboratories missed the same mutation in all three rounds indicating an assay failure and results from a further three laboratories suggested an issue with assay validation, write Simon Patton et al.

While all 17 laboratories improved their performance in the third round of testing compared with round two, just six laboratories gave correct results for all 10 samples and four failed the EQA.

While the overall standard of EGFR testing was “acceptable”, the researchers say the findings “underline the importance of EQA as a mechanism to reveal errors in methodology and to ensure an adequate quality of molecular testing.”

They conclude: “Regular participation in EQA should be seen as a routine part of the diagnostic testing process for all labs helping to improve and standardise their processes.”


Patton S, Normanno N, Blackhall F, et al. Assessing standardization of molecular testing for non-small-cell lung cancer: results of a worldwide external quality assessment (EQA) scheme for EGFR mutation testing. Br J Cancer 2014; Advance online 1 July. doi: 10.1038/bjc.2014.353

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