Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review

James Sherwood, Simon Dearden, Marianne Ratcliffe, Jill Walker, James Sherwood, Simon Dearden, Marianne Ratcliffe, Jill Walker

Abstract

Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both primary and metastatic tumour sites to accurately reflect the tumour mutation status will allow more patients to receive therapies personalised to their disease.

Figures

Fig. 1
Fig. 1
Study selection flow diagram. Literature searches carried out on 25 July 2013, 3 January 2014 and 8 September 2014
Fig. 2
Fig. 2
EGFR mutation pattern in 56 primary tumour and 30 lymph node metastasis sites obtained from nine patients with EGFR-mutant lung adenocarcinomas. A homogeneous mutation pattern was detected in five primary tumours (cases 2, 3, 4, 7 and 9) and all but one (case 6) metastasis case. Case 6 had mixed wild-type and mutant sites in both primary tumour sites and corresponding metastases. EGFR, epidermal growth factor receptor. Reprinted from Cancer Prev Res (Phila), 2008, 1, 192–200, Tang et al., Epidermal growth factor receptor abnormalities in the pathogenesis and progression of lung adenocarcinomas, with permission from AACR [60]

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