Toward a Molecular Classification of Synchronous Colorectal Cancer: Clinical and Molecular Characterization

Abstract

Background: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood.

Patients and methods: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor. We considered Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis (MAP) as exclusion criteria.

Results: Molecular subgrouping on the basis of MSI and CIMP enabled us to define 4 groups that corresponded to the molecular classification proposed for single-tumor CRC. We observed a significant predominance of MSI tumors at the right side regardless of the methylation pattern, and a significant prevalence of microsatellite-stable tumors either at the left side or throughout the entire colon (P = .026). Furthermore, we defined some molecular features frequently observed in sporadic SCRC such as a low-frequency of MSI (8.2%). We observed a high concordance in terms of MSI between simultaneous tumors (93.9%) and a lower concordance in terms of CIMP (51%) between such tumors.

Conclusion: Our findings support the hypothesis that SCRC involves an environmental rather than a genetic component in which various etiologic factors might modify tumor progression. Further studies are required to refine the molecular characterization of SCRC.

Keywords: CpG island methylator phenotype; Microsatellite instability; Promoter methylation; Synchronous colorectal cancer; Tumor location.