Clinicopathological and Molecular Characterization of Non-Endometrioid Endometrial Carcinoma

Objective: Molecular classification has become an essential tool in endometrial carcinoma; however, its application in non-endometrioid carcinoma (NEEC), particularly rare histological subtypes, remains relatively unexplored. This study aims to investigate the potential utility of molecular classification in NEEC. Methods: A retrospective analysis was conducted on 167 NEEC cases diagnosed at the Women's Hospital of Zhejiang University from 2013 to 2020. The cases were categorized into four molecular subtypes: POLE ultra-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-abnormal (p53abn), and no specific molecular profile (NSMP) molecular subgroups. Statistical significance was set at P<0.05. Results: Among the cases, 13 (7.8%) patients were classified as POLEmut, 25 (15.0%) as MMRd, 84 (50.3%) as p53abn, and 45 (27.0%) as NSMP. Most POLEmut cases were at early stages (11/13, 84.6% at stages I-II), whereas p53abn cases were predominantly at advanced stages (32/49, 65.3% at stages III-IV). Additionally, p53abn was the most common subtype in serous carcinoma (41/45, 91.1%) and mixed adenocarcinoma (24/57, 42.1%). The 3-year recurrence-free survival (RFS) rates for POLEmut, MMRd, NSMP, and p53abn were 100.0%, 88.0%, 73.3%, and 71.4% , respectively. The 3-year overall survival (OS) rates were 100.0%, 88.0%, 82.2%, and 73.8%, respectively. Univariate analysis revealed significant associations of age ≥60 years (P=0.01), hypertension (P=0.03), FIGO stage (P<0.001), lymphovascular space invasion (P=0.01), lymph node metastasis (P<0.001), myometrial invasion (P<0.001), and postoperative adjuvant therapy (P=0.01) with 3-year RFS. Multivariate analysis identified age ≥60 years (P=0.03), myometrial invasion (P=0.01), and FIGO stage (P=0.046) as independent risk factors for 3-year OS. Conclusion: Molecular classification is crucial for accurately predicting the prognosis of NEEC, enabling more tailored treatment approaches in clinical practice. Furthermore, patient age may have a significant influence on NEEC classification and progression.