Observational studyInternational journal of clinical oncology2026
Prevalence and clinicopathologic features of mismatch repair-deficient endometrial cancer in Japanese patients younger than 50 years: a single-center prospective observational study.
Observational study in International journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundUniversal tumor testing is increasingly recommended for Lynch syndrome (LS). However, data involving younger Japanese patients are still limited. This study aimed to prospectively evaluate the prevalence and clinicopathologic profile of DNA mismatch repair (MMR)-deficient (dMMR) endometrial cancers (EC) in patients aged under 50 years, and characterize immunohistochemical (IHC) loss patterns and genetic testing results.
methodsPatients with EC aged under 50 years who consented to study participation were prospectively enrolled at a single Japanese institution. Diagnostic specimens underwent MMR IHC (MLH1, MSH2, MSH6, and PMS2). Clinicopathologic variables were compared between proficient MMR (pMMR) and dMMR.
resultsAmong 111 patients, 26 (23.4%) had dMMR. Grades differed when dichotomized as G1 versus G2-G3 (p < 0.01). FIGO stage distribution also varied between groups (p = 0.035). Among dMMR tumors, IHC patterns were loss of MLH1/PMS2 (n = 12), loss of MSH2/MSH6 (n = 8), and isolated loss of MSH6 (n = 6). Of the 12 (46.2%) patients with dMMR who underwent germline testing, 9 had LS (MLH1/PMS2 loss: 3/5; MSH2/MSH6 loss: 4/4; MSH6 isolated loss: 2/3). The overall dMMR prevalence in this young cohort was comparable to that in all-age series from multiple regions. This represents a minimum prevalence of LS in the overall study cohort, as germline testing was performed only in a subset of patients with dMMR tumors.
conclusionsIn this prospective Japanese cohort, approximately one in four patients with EC had dMMR, with clinicopathologic features skewing toward a higher grade. Notably, many dMMR tumors were grade 2-3, suggesting that a substantial proportion of patients may fall outside the conventional criteria for fertility-sparing treatment.
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