Discordance Between Clinicopathological and Molecular Risk Classification in Endometrial Carcinoma: A Prospective Observational Study

Background: Endometrial carcinoma is commonly managed using clinicopathological risk stratification to guide adjuvant treatment. However, p53 and mismatch repair (MMR) status may identify biological risks not captured by conventional classifications. Local evidence regarding discordance between clinicopathological and molecular risk profiles remains limited. This study aimed to assess this discordance and to describe treatment allocation and one-year outcomes among patients with molecular abnormalities. Methods: This prospective observational study was conducted at the National Institute of Cancer Research and Hospital, Dhaka, from October 2021 to May 2023 and included 42 women with endometrial carcinoma who underwent definitive surgery. Risk was assigned by the ESGO/ESTRO/ESP 2021 consensus, p53 and MMR proteins were assessed by immunohistochemistry and patients were followed for one year. Fisher's exact test was used for outcome comparisons. Results: Conventional classification identified 17 low-risk (40.5%) and 18 high-risk (42.9%) patients, with seven in intermediate categories. Abnormal p53 expression was found in five patients (11.9%) and MMR deficiency in 16 (38.1%). Among the 17 low-risk patients, one (5.88%) had abnormal p53 and seven (41.17%) were MMR deficient; among the 18 high-risk patients, four (22.2%) had abnormal p53 and five (27.78%) were MMR deficient. No low-risk patient with a molecular abnormality received adjuvant treatment or progressed. Freedom from progression was 60.0% with abnormal p53 versus 97.3% with normal p53 (p=0.001) and 93.8% versus 92.3% for MMR-deficient and MMR-retained tumours (p=0.414). Conclusion: Molecular abnormalities occurred in conventionally low-risk endometrial carcinoma, indicating that clinicopathological classification alone does not capture molecular risk. Combined assessment may refine risk stratification, pending larger confirmatory studies.