The relationship between histopathological data and molecular alterations with oncological outcomes in endometrioid-type endometrial cancers and a novel POLE mutation


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Aksahin E., DEMİRKIRAN F., Bese T., Cebi S., AÇIKGÖZ A. S., Kayan B. O., ...Daha Fazla

Journal of Gynecologic Oncology, cilt.37, sa.1, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3802/jgo.2026.37.e6
  • Dergi Adı: Journal of Gynecologic Oncology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: Endometrioid Type Endometrium Cancer, MMR-d, Molecular Classification, p53, POLE
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Objective: To identify molecular subgroups in endometrioid endometrial cancer (EEC), evaluate their association with clinicohistopathological characteristics, and define low-intermediate risk groups by integrating these parameters. Methods: This retrospective-cohort study included 1,040 patients who underwent surgery between January 2000 and June 2022. Among 900 EEC cases, 72 recurred. Patients with tumor recurrence (n=62) and those without (n=52) were matched. POLE exons 9–14 were examined using Sanger sequencing. p53 and mismatch repair (MMR) protein expression were assessed via immunohistochemistry. Results: The molecular subgroups were POLE mutation (POLE-mut) 5%, mismatch repair-deficient (MMR-d) 43%, p53 mutation (p53-mut) 5%, and non-specific molecular profile (NSMP) 42%. 5% of cases displayed multiple molecular mutations. POLE-mut were more prevalent in high-grade tumors (p=0.026). MMR-d tumors exhibited higher rates of lymphovascular space invasion and myometrial invasion ≥50% (p=0.032, p=0.020). No recurrences occurred in POLE-mut tumors (p=0.002), while MMR-d was significantly associated with recurrence (p=0.002). Median disease-free survival (DFS) for MMR-d, p53-mut, and NSMP were 34, 49, and 107 months, respectively. Median overall survival (OS) for these groups was 128, 102, and 181 months. Multivariate Cox-regression analysis employing the Backward-Stepwise method identified stage as the strongest predictor of DFS, and grade and stage as predictors of OS. Conclusion: POLE mutations were linked to the most favorable molecular prognostic factor. NSMP cases showed the longest DFS and OS, while p53-mut had the shortest OS. Except for POLE, molecular features alone were insufficient for establishing risk groups, highlighting the continued importance of histopathology in EEC management.