Synchronous and metachronous primary colorectal cancers with concordant and discordant mismatch repair status

Abstract

Multiple primary colorectal carcinomas (CRCs) synchronous, when detected approximately at the same time, or metachronous, when a significant amount of time has elapsed between diagnoses can show both mismatch repair (MMR) status concordance and discordance between primary tumors. The aim was to evaluate the MMR status of a monoinstitutional, retrospective cohort of synchronous and metachronous CRCs, with a focus on the frequency of cases with discordant MMR status, and explore the MMR status of metastatic nodal deposits. All synchronous and metachronous CRCs diagnosed in our institution between 2011 and 2023 were collected. Clinicopathologic characteristics were evaluated, including MMR status of all CRCs, BRAF mutation, and MLH1 promoter methylation analyses. MMR status discordant cases were further analyzed, and MMR testing was performed on nodal metastases. Of 3671 patients, 107 (2.9%) had multiple CRCs (94 synchronous and 13 metachronous; total number of CRCs 220). Sixty CRCs were MMR deficient (dMMR) (27.3%), and most were right-sided and high-grade and showed special histologic features (P < .00001). Ninety-three patients showed intertumoral MMR concordance: 70 (65.4%) with MMR-proficient (pMMR) CRCs, and 23 (21.5%) were dMMR. Fourteen patients (13.1%) showed intertumoral MMR discordance (at least one dMMR and one pMMR), and in 5 patients, nodal metastases were present: 2 patients harbored metastases only from their pMMR cancer, 2 only from their dMMR cancer, and in 1 patient both pMMR and dMMR metastases were present. In conclusion, all multiple primary CRCs should be analyzed for MMR status as discordant MMR is possible as well as discordant metastatic nodal deposits, and this may be important for patient management.

Keywords: Colorectal cancer; Lynch syndrome; Metachronous cancer; Microsatellite instability; Mismatch repair; Synchronous cancer.