Franques Paul, Moreau Pierre, Evrard Camille, Chong-Si-Tsaon Arnaud, Frouin Éric, Auriault Marie-Luce, Moulin Valérie, Junca Audelaure, Godet Julie, Lebeau Lucie, Aguillon Roxane, Tachon Gaëlle, Karayan-Tapon Lucie, Tougeron David
Medical Oncology Department, Poitiers University Hospital, Poitiers, France.
ProDiCeT, UR 24144, University of Poitiers, Poitiers, France.
Therap Adv Gastroenterol. 2025 Jun 21;18:17562848251347375. doi: 10.1177/17562848251347375. eCollection 2025.
Colorectal cancers (CRC) with deficient mismatch repair system and/or microsatellite instability-high (dMMR/MSI-H) phenotype represent about 12% of CRC. dMMR/MSI-H CRC is due to a germline mutation (Lynch syndrome, LS) or an age-related epigenetic mechanism, mostly by hypermethylation of 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.
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.
We used a prospective cohort of 484 well-characterized patients with dMMR/MSI-H CRC to describe their risk of having APC.
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.
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.
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.
错配修复缺陷系统和/或微卫星高度不稳定（dMMR/MSI-H）的结直肠癌（CRC）约占CRC的12%。dMMR/MSI-H CRC是由种系突变（林奇综合征，LS）或与年龄相关的表观遗传机制引起的，主要是启动子的高甲基化（散发性病例）。众所周知，LS患者一生中患各种dMMR/MSI-H癌症的风险很高，但关于散发性dMMR/MSI-H CRC患者发生第二种癌症的风险尚无数据。
本研究的主要目的是确定dMMR/MSI-H CRC患者发生另一种原发性癌症（APC）的风险。我们还收集了这些肿瘤以确定其MMR表型。
我们使用了一个前瞻性队列，其中包括484例特征明确的dMMR/MSI-H CRC患者，以描述他们发生APC的风险。
我们根据LS与散发性状态评估了APC的发生情况（在dMMR/MSI-H CRC发生之前或之后），无论分期或肿瘤部位如何。比较了有和没有APC的两组以及LS与散发性状态的特征。
在484例dMMR/MSI-H CRC患者中，我们确定了116例有既往或第二种原发性肿瘤的患者（24.0%），除dMMR/MSI-H CRC外，每位患者平均有1.4个肿瘤。最常见的肿瘤部位是皮肤（24.7%）和乳腺（18.5%）。关于APC的发生情况，我们发现与LS相关的dMMR/MSI-H CRC组患者（25.0%）和散发性dMMR/MSI-H CRC患者（24.8%）之间没有差异。在我们的队列中，无论是LS还是散发性病例亚组，没有危险因素与APC的发生相关。在散发性组中，3.8%的APC具有dMMR/MSI-H表型，而在LS组中这一比例为50.0%。
由于发生第二种肿瘤的风险很高，即使在散发性病例中，对有dMMR/MSI-H CRC病史的患者进行随访似乎也很重要。散发性dMMR/MSI-H CRC患者的第二种癌症很少与dMMR/MSI-H表型相关。
