Tumor Grade and Molecular Prognostic Markers in Endometrial Carcinoma: A Systemic Review & Meta Analysis

Abstract

Background: Endometrial carcinoma (EC) is a biologically heterogeneous malignancy in which traditional histopathological grading alone does not reliably predict clinical outcomes. Recent advances in molecular classification have introduced novel prognostic markers that may refine risk stratification.Objective: To evaluate the correlation between tumor grade, key molecular markers, and survival outcomes in patients with endometrial carcinoma through a systematic review and meta-analysis.Methods: A comprehensive literature search was performed across PubMed, Scopus, Embase, and Web of Science up to January 2026. Studies assessing tumor grade in conjunction with molecular markers-primarily POLE mutations, mismatch repair deficiency (MMRd), and p53 abnormalities-and reporting survival outcomes were included. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using a random-effects model.Results: Thirty-eight studies comprising 12,450 patients were included. High tumor grade (Grade 3) was significantly associated with poorer overall survival (HR 2.14, 95% CI 1.78–2.56) and progression-free survival (HR 1.96, 95% CI 1.61–2.38). Molecular classification revealed distinct prognostic groups: POLE-mutated tumors demonstrated excellent prognosis (HR 0.45), MMR-deficient tumors showed intermediate outcomes (HR 0.89), while p53-abnormal tumors were associated with the worst survival (HR 2.76). Integrated analysis combining tumor grade with molecular markers significantly improved prognostic accuracy compared to grading alone.Conclusion: Molecular markers provide superior prognostic stratification over conventional tumor grading in endometrial carcinoma. The integration of histopathological and molecular classification should be adopted in routine clinical practice to enable more precise, individualized patient management.