Role of Serum HE4, Selected Clinical Features and Diagnostic Prediction Models in Differentiating Benign and Malignant Endometrial Lesions in Polish Women: A Prospective Cohort Study

Background/Objectives: The differentiation of endometrial cancer from non-malignant endometrial findings remains clinically important. We evaluated serum human epididymis protein 4 (HE4), clinical and ultrasound features, and two published diagnostic models, the Risk of Endometrial Malignancy (REM) score and Model A. Methods: In this prospective cohort, 110 women with abnormal uterine bleeding and/or ultrasound abnormalities underwent HE4 testing, transvaginal ultrasonography, and hysteroscopy with histopathological assessment. Original univariable analyses were supplemented by reanalysis of the individual study records, including ROC metrics, paired comparisons of AUCs, and an exploratory logistic model adjusting for age and endometrial thickness. Results: Endometrial cancer was diagnosed in 18 women; 92 had non-malignant findings. Median HE4 was higher in the cancer group (118.35 versus 52.3 pmol/L; p < 0.001, as originally reported). The AUC (95% bootstrap CI) was 0.834 (0.686–0.951) for HE4, 0.905 (0.794–0.981) for REM, and 0.840 (0.702–0.948) for Model A. AUC differences were not statistically significant (paired DeLong tests, all p > 0.10). In an exploratory adjusted analysis, each doubling of HE4 was associated with higher odds of malignancy (adjusted OR 5.41; 95% CI 1.81–16.21; p = 0.0025). Conclusions: HE4 and both published models discriminated between malignant and non-malignant findings in this selected cohort. The findings are exploratory and require independent validation before clinical use.