Prevalence and Clinical Implications of Mismatch Repair-Proficient Colorectal Cancer in Patients With Lynch Syndrome
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Le résumé fourni par la source
PURPOSE Lynch syndrome (LS)–associated colorectal cancer (CRC) is characterized by mismatch repair-deficiency (MMR-D) and/or microsatellite instability (MSI). However, with increasing utilization of germline testing, MMR-proficient (MMR-P) and/or microsatellite stable (MSS) CRC has also been observed. We sought to characterize MMR-P/MSS CRC among patients with LS. METHODS Patients with solid tumors with germline MMR pathogenic/likely pathogenic (P/LP) variants were identified on a prospective matched tumor-normal next-generation sequencing (NGS) protocol. CRCs were evaluated for MMR-D via immunohistochemical (IHC) staining and/or MSI via NGS. Clinical variables were correlated with MMR status using nonparametric tests. RESULTS Among 17,617 patients with solid tumors, 1.4% (n = 242) had LS. A total of 36% (86 of 242) of patients with LS had at least one CRC that underwent NGS profiling, amounting to 99 pooled CRCs assessed. A total of 10% (10 of 99) of CRCs were MMR-P, with 100% concordance between MSS status and retained MMR protein staining. A total of 89% (8 of 9) of patients in the MMR-P group had MSH6 or PMS2 variants, compared with 30% (23 of 77) in the MMR-D group ( P = .001). A total of 46% (6 of 13) of PMS2+ patients had MMR-P CRC. The median age of onset was 58 and 43 years for MMR-P and MMR-D CRC, respectively ( P = .07). Despite the later median age of onset, 40% (4 of 10) of MMR-P CRCs were diagnosed <50. A total of 60% (6 of 10) of MMR-P CRCs were metastatic compared with 13% (12 of 89) of MMR-D CRCs ( P = .002). A total of 33% (3 of 9) of patients with MMR-P CRC did not meet LS testing criteria. CONCLUSION Patients with LS remained at risk for MMR-P CRC, which was more prevalent among patients with MSH6 and PMS2 variants. MMR-P CRC was later onset and more commonly metastatic compared with MMR-D CRC. Confirmation of tumor MMR/MSI status is critical for patient management and familial risk estimation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Prevalence and Clinical Implications of Mismatch Repair-Proficient Colorectal Cancer in Patients With Lynch Syndrome
- Date Crossref
- 01/05/2023
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Memorial Sloan Kettering Cancer Center pays non établi dans la noticeÉtablissement de santé
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Cornell University pays non établi dans la noticeUniversité ou école supérieure
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Molecular Oncology (United States) pays non établi dans la noticeEntreprise
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Department of Medicine pays non établi dans la noticeInstitution
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Niehaus Center for Inherited Cancer Genomics pays non établi dans la noticeInstitution
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Department of Pathology pays non établi dans la noticeInstitution
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Department of Surgery pays non établi dans la noticeInstitution
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Weill Cornell Medical College Department of Surgery pays non établi dans la noticeUniversité ou école supérieure
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Marie-Josée and Henry R. Kravis Center for Molecular Oncology pays non établi dans la noticeInstitution
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Human Oncology and Pathogenesis Program pays non établi dans la noticeInstitution
Memorial Sloan Kettering Cancer Center, Cornell University et Molecular Oncology (United States), avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.