Differences in clinical characteristics and mutational pattern between synchronous and metachronous colorectal liver metastases

PURPOSE: To investigate differences in clinical characteristics and mutational patterns between synchronous and metachronous colorectal liver metastases (CLMs). PATIENTS AND METHODS: From June 2008 to December 2014, patients with RAS wild-type CLMs treated at Zhongshan Hospital, Fudan University were included. DNA extracted from formalin-fixed paraffin-embedded tissue of primary tumors was sequenced with next-generation sequencing for single-nucleotide polymorphism of 96 genes according to custom panel. Mutations were compared between synchronous and metachronous liver metastases and correlated with clinical characteristics. RESULTS: A total of 161 patients were included: 93 patients with synchronous CLM and 68 patients with metachronous CLM. Patients with metachronous CLM were obviously elder. For pathology of primary tumors, synchronous CLMs were larger in size, poorly differentiated, and more frequently local advanced and lymph node positive. For evaluation of liver metastases, synchronous CLM had more and larger metastatic lesions. The median number of mutations in synchronous CLMs was significantly higher than in metachronous group (22 vs. 18, p<0.001). EGFR rs2227983 is the most prevalent mutation in both groups and only a part of prevalent mutations is shared in both groups. Prevalent mutations were correlated with many clinical characteristics. EGFR rs2227983, RBMXL3 rs12399211, and PTCH1 rs357564 were prognostic for latency of metachronous CLM. CONCLUSION: Clinically, synchronous CLMs, compared with metachronous CLMs, were younger and showed heavier tumor burden for both primaries and liver metastases. Genetically, we identified different mutational patterns between synchronous and metachronous CLMs and several correlations between mutations and clinical characteristics. Further researches were needed to confirm these potential key mutations of CLMs.