OBJECTIVES: To investigate the relationship between mismatch repair (MMR) deficiency, TP53, and L1 cell adhesion molecule (L1CAM) immunohistochemical staining and their impact on progression-free survival (PFS) and overall survival (OS) in low-risk endometrial cancer. MATERIAL AND METHODS: A total of 253 low-risk endometrial cancer patients were retrospectively screened. Immunohistochemical stains were applied to tumor tissue samples to assess MMR deficiency, TP53, and L1CAM expression, and survival analysis were performed. RESULTS: The expected PFS time was 78.6 months for the MMR-proficient group and 70.3 months for the MMR-deficient group (p = 0.011). OS was 71.6 months for the MMR-proficient group and 68.2 months for the MMR-deficient group (p = 0.755). L1CAM overexpression was associated with a poorer PFS, 62.7 months compared to 77.7 months (p = 0.039). However, there was no statistically significant difference in OS, 58.5 months versus 72.1 months, respectively (p = 0.242). p53 abnormal (p53-abn) staining was associated with a worse prognosis in terms of PFS, 62.8 months versus 77.7 months (p = 0.035), and OS, 43.4 months versus 73 months, respectively (p <
0.001), compared to patients with wild-type staining. No significant statistical relationship was observed in survival times concerning tumor diameter, grade, and lymphadenectomy status. In a multivariate analysis, MMR deficiency emerged as an independent poor prognostic factor for PFS, while p53-abn was identified as an independent poor prognostic factor for OS. CONCLUSIONS: p53-abn staining was associated with a poor prognosis for both PFS and OS in low-risk endometrial cancer patients. Meanwhile, MMR deficiency and L1CAM positivity were found to be associated solely with a poorer prognosis for PFS.