What specimen types are suitable for mutation testing in NSCLC patients?
Systematic Review Evidence
Advanced stage lung adenocarcinomas, NSCLC with any glandular differentiation or NSCLC, not otherwise specified, all require mutation testing to assess for targetable mutations in the epidermal growth factor receptor (EGFR) gene or translocations involving the anaplastic lymphoma kinase (ALK) gene. This information is required to help determine the most appropriate 1st line treatment due to the availability of tyrosine kinase inhibitors that specifically target these alterations. Pathologists and treating physicians need to know which specimens are suitable for mutation testing to ensure the mutation status of each patient’s tumour is accurately determined.
Most studies compared the concordance of mutation status in tissue samples obtained from primary tumours versus metastases; or the mutation status in histology tissue samples versus cytology samples. While there was generally high concordance across the different groups in keeping with the underlying biology of these genetic alterations as driver alterations, slightly lower rates of mutations were sometimes found in samples obtained from metastatic tumours compared to primary tumours, possibly relating to technical factors such as smaller tumour samples from these sites. Little information was provided on the sample size, quantity or proportion of tumour cells which could all effect the results. Lower concordance was also generally found when lower sensitivity techniques were used to assess mutation status. To avoid false negatives, primary tumours or samples with the greatest tumour volume should be used for mutation testing where available. In the setting of EGFR mutant tumours that have developed resistance to an EGFR-TKI, repeat testing may be undertaken to assess for acquisition of targetable resistance mutations (such as EGFR T790M mutation) and tissue or “liquid biopsy” specimens (circulating tumour DNA in plasma) could potentially be used, however, this was not specifically addressed in the literature review.
Evidence summary and recommendations
|There is generally high concordance in the mutation status of tumours obtained by using samples from histology or cytology samples, or from primary tumours versus metastases||III-1, III-2||, , |
|Any tumour sample can be used for mutation testing (sample from primary or metastatic site; histology or cytology sample).||C|
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