Guangwei Yan

Effects of Adjuvant Radiation Plus Chemotherapy on Survival Outcomes in Stage III C Endometrial Cancer According to Histology: Analysis of Data from the Surveillance, Epidemiology, and End Results Database

Purpose: To evaluate the survival benefit of radiation plus chemotherapy in adult females with stage IIIC endometrial cancer and to investigate whether the benefit varies according to histology. Methods: Data from adult females with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC endometrial cancer, who underwent at least total hysterectomy between 2010 and 2015, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Adjuvant treatments were categorized as chemotherapy alone, chemotherapy with external beam radiation therapy (EBRT), chemotherapy with vaginal brachytherapy (VBT), or chemotherapy with EBRT+VBT. Multivariate Cox regression models, Kaplan–Meier curves, and log-rank tests were used to assess the association between treatment modality and overall survival (OS). Results: In total, 2138 cases were identified: stage IIIC1 (n = 1299 [60.8%]) and stage IIIC2 (n = 839 [39.2%]). Median OS for all patients was 48 (interquartile range [IQR] 28-70) months. Regarding adjuvant treatment, 40.5% of patients underwent chemotherapy only, followed by chemotherapy with EBRT (35.5%). Stage IIIC patients treated with chemotherapy plus radiation exhibited a significantly reduced risk for death from endometrial cancer in both univariate and multivariate analyses ( P < 0.001). However, when stratified according to histology, OS also differed according to treatment modality when analyzing each histological type; combination therapy was no longer significantly different from chemotherapy alone for any histology (clear cell and carcinosarcoma). Combination therapy was associated with improved OS in patients with IIIC1 and IIIC2 disease. Similar associations were observed in patients with high-grade stage IIIC endometrioids. However, for low-grade tumors, combination therapy was no longer associated with reduced risk for death compared with chemotherapy alone. Conclusion: For patients with stage IIIC endometrial cancer, combined treatment with radiation and chemotherapy was associated with improved OS compared with chemotherapy alone. However, no survival benefit was found, and radiotherapy may be unnecessary in patients with low-grade endometrioids.

Universal screening for Lynch syndrome and molecular classification of patients with endometrial cancer

Objective: Lynch syndrome (LS) is a cancer susceptibility syndrome characterized by a high risk table of multiple cancer types, most commonly endometrial cancer (EC). Currently, universal tumor screening to identify LS in women with EC remains uncommon. This study aimed to determine the incidence of LS and its molecular landscape by conducting a retrospective analysis of a cohort of patients with EC in China. Methods: A total of 220 patients with EC were identified from the Hospital between March 2022 and May 2025. Germline variants in LS-associated genes ( MLH1, PMS2, MSH2, MSH6 , and EPCAM ) and molecular subtypes [ POLE, TP53 genes, and microsatellite instability (MSI)] were analyzed using next-generation sequencing (NGS). Mismatch repair (MMR) proteins were screened by immunohistochemistry (IHC). Tumors with loss of MLH1 or MLH1/PMS2 protein expression were tested for MLH1 promoter methylation. Results: Of the 220 cases, 16 (7.3%) had a pathogenic germline variant in MMR genes, with the majority identified in MSH6 ( n = 7), followed by MLH1 ( n = 3), PMS2 ( n = 3), and MSH2 ( n = 3). A total of 22 EC tumors (10.0%) carried a variant of uncertain significance in the LS-associated genes. Our results revealed that the percentages of the different molecular subtypes were POLE-mutated (POLEmut; 10.9%), mismatch repair deficient (MMRd; 25.5%), p53 abnormal (p53abn; 8.6%), and no specific molecular profile (NSMP; 55.0%). Ten “multiple-classifier” tumors (4.5% of the total cases) were identified. These included five MMRd-p53abn, four POLEmut-p53abn, and one POLE-MMRd. Conclusion: This study confirms the effectiveness of NGS in identifying germline variants within a Chinese cohort of patients with EC, revealing an LS prevalence of 7.3%. Relying solely on MMR-IHC or MSI testing could lead to missed diagnoses of LS. Our findings contribute to a better understanding of the mutational landscape and prevalence of LS.