Second malignancies in patients with deficient mismatch repair system/microsatellite instability-high colorectal cancer

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Background: promoter (sporadic cases). It is well recognized that patients with LS have a high lifetime risk of various dMMR/MSI-H cancers, but there are no data concerning the risk of a second cancer in sporadic dMMR/MSI-H CRC. Objectives: The main objective of this study was to determine the risk of having another primary cancer (APC) in patients with dMMR/MSI-H CRC. We also collected these tumors to determine their MMR phenotype. Design: We used a prospective cohort of 484 well-characterized patients with dMMR/MSI-H CRC to describe their risk of having APC. Methods: We evaluated the occurrence of APC (before or after the occurrence of the dMMR/MSI-H CRC) according to LS versus sporadic status, whatever the stage or the tumor site. The characteristics of the two groups, with and without APC, and LS versus sporadic status were compared. Results: Among the 484 patients with dMMR/MSI-H CRC, we identified 116 patients with a previous or a second primary tumor (24.0%), with an average of 1.4 tumors per patient in addition to the dMMR/MSI-H CRC. The most frequent tumor sites were skin (24.7%) and breast (18.5%). Regarding the occurrence of APC, we found no difference between patients with LS-related dMMR/MSI-H CRC group (25.0%) and those with sporadic dMMR/MSI-H CRC (24.8%). No risk factor was associated with the occurrence of APC in our cohort, in the LS or sporadic cases subgroup. In the sporadic group, 3.8% of APC had a dMMR/MSI-H phenotype as compared to 50.0% in the LS group. Conclusion: It seems important to follow patients with a history of dMMR/MSI-H CRC due to the high risk of second tumors, even in sporadic cases. Second cancers in patients with sporadic dMMR/MSI-H CRC are rarely associated with a dMMR/MSI-H phenotype.

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