High mutational concordance between primary colorectal tumors and associated pulmonary metastases

Abstract

Background and Objectives: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not welldescribed. This study aims to determine the concordance of genomic profiles between primary CRC and PM.Methods: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. Results: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. Conclusions: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy. K E Y W O R D S colorectal cancer, concordance, genes, mutations, pulmonary metastases F I G U R E 2 Mutational concordance by a gene with concordant specimens in light/dark blue and discordant samples in light/dark red. WT, wild-type [Color figure can be viewed at wileyonlinelibrary.com] 986 | CORSINI ET AL. CONFLICT OF INTERESTSThe authors declare that there are no conflict of interests. DATA AVAILABILITY STATEMENTDeidentified patient data, as well as plan of statistical analyses, which underlie the results reported in this investigation will be made available upon request immediately upon publication for up to 36 months. Requests from investigators with methodologically sound research proposals will be granted for specific analyses outlined within such proposals or meta-analyses.Requests for data sharing should be submitted to the corresponding author. ORCIDErin M. Corsini http://orcid.org/0000-0003-4715-0244 988 | CORSINI ET AL.