Abstract
INTRODUCTION: Endometrial cancer (EC) is the sixth most frequent female malignancy worldwide. Atypical endometrial hyperplasia (AEH), also termed endometrial intraepithelial neoplasia (EIN), represents the recognized precursor lesion. While hysteroscopy with biopsy remains the diagnostic gold standard, the lack of non-invasive biomarkers for early detection and follow-up is a major clinical limitation. MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have emerged as potential diagnostic and prognostic tools in gynecological oncology. OBJECTIVE: We aimed to determine the accuracy of the predictive value of a selected panel of miRNAs (miR-504-5p and miR-429) obtained on endometrial samples, in detecting EC and EIN, and to explore their role along the neoplastic continuum. METHODS: A prospective observational study was conducted at the University of Naples "Federico II." Thirty-seven patients were enrolled: EC (n = 15), EIN (n = 15), and controls with normal endometrium (n = 7). All underwent hysteroscopy with grasp biopsy or "Visual D&C." Formalin-fixed paraffin-embedded samples were processed for RNA extraction, and miRNA expression was analyzed by RT-PCR (Taqman Advanced miRNA Assays). RESULTS: Both miRNAs were successfully amplified in most cases. In EC, miR-504-5p was detected in 93.3 % and miR-429 in 100 % of samples, with mean Ct values of 32.2 and 29.7, respectively. AEH showed intermediate expression (93.3 % and 86.7 % detection rates; mean Ct 28.3 and 29.8). Normal endometrium displayed the highest expression (100 % and 85.7 %; mean Ct 25.5 and 26.8). A progressive downregulation of both miRNAs from normal tissue to AEH and EC was observed. CONCLUSION: Our preliminary findings suggest that reduced expression of miR-504-5p and miR-429 characterizes the transition from EIN to EC, supporting their potential role as tumor suppressors in this setting. This two-miRNA panel could complement histopathology in distinguishing precursor lesions from carcinoma, addressing a key diagnostic challenge. Larger studies, including minimally invasive liquid biopsy approaches, are warranted to validate their clinical utility.