Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia

Background: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. Methods: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAF c.1799T>A mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. Results: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P =0.001) and with HNPCC (9/32, 28%, P