Clinicopathological and molecular profiling of sporadic synchronous multiple primary colorectal cancers: focus on microsatellite instability status

Background: Sporadic synchronous multiple primary colorectal cancer (SSCRC) is uncommon, and its molecular features remain unclear. This study aimed to compare the clinicopathological and molecular characteristics of SSCRC with solitary colorectal cancer and to evaluate microsatellite instability (MSI) status across synchronous lesions.

Methods: We retrospectively enrolled 46 patients with synchronous CRCs and 202 patients with solitary CRCs. MSI status was determined for each SSCRC lesion using polymerase chain reaction (PCR)-based testing. Additional clinicopathological variables and selected molecular features were also assessed.

Results: Compared with solitary CRC, SSCRC index lesions were associated with more advanced clinicopathological features (all P<0.05). The proportion of deficient mismatch repair (dMMR) was significantly higher in SSCRC (19.6% vs. 5.0%, P=0.003). Overall survival was significantly worse in SSCRC (P=0.03), while disease-free survival did not differ significantly between groups. All SSCRC cases demonstrated concordant MSI status across lesions, with 19.6% classified as MSI-H and 80.4% as MSI-L/MSS.

Conclusions: MSI status appears central to SSCRC biology and may aid prognostic stratification. SSCRC exhibits distinct clinicopathological and molecular characteristics relative to solitary CRC, supporting the need for lesion-level molecular evaluation to inform personalized management. In particular, patients with dMMR tumors may benefit from immunotherapy, highlighting the clinical importance of MSI assessment.