Serum HE4 as a Preoperative Predictor of Myometrial Invasion and Risk Stratification in Endometrial Carcinoma: Comparison with histopathology

Background: Endometrial cancer is one of the common female genital tract cancers in developed countries. Human epididymis protein 4 (HE4) is known as whey acidic protein. Elevated levels of HE4 in the blood or tissue can be associated with several malignancies, making it a potential biomarker for cancer detection and monitoring. Objective: This study was conducted to determine the predictive value of serum HE4 as a pre-operative biomarker for myometrial invasion and risk categorization in endometrial carcinoma, comparing its performance with histopathological assessment. Methods: This was a cross-sectional analytical study conducted at the Department of Gynecological Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from July 2022 to June 2023. In this study, we included 40 women with a diagnosed case of endometrial cancer who were admitted to the Department of Gynecological Oncology at our institution. Results: The study revealed, the majority of patients were in the 55-64 years age group, with post-menopausal bleeding being the most common symptom (82.5%). The mean duration of symptoms was 6.0±3.79 months. A significant proportion of patients were obese (42.5%). In terms of contraceptive use, most respondents (85.5%) were not using any contraceptive method, while 12.5% used oral contraceptive pills. Family history of first-degree relatives with cancer was found in 5% of the study subjects. A predominant histopathological type of endometrial cancer was endometrioid adenocarcinoma, accounting for 85.0% of the cases, and approximately one-third of the study subjects (32.5%) were classified as stage IA. In terms of risk categorization, 60.0% were classified into the high-risk group, 22.5% into the intermediate-risk group, and 17.5% as low-risk individuals. Serum HE4 levels exhibited a significant association with histopathological grade (p = 0.031) and more extensive myometrial invasion (>50%) (p < 0.001). The mean HE4 level was significantly lower in the low-intermediate risk group than the high-risk groups (94.88±29.28 vs. 136.06±62.98 pmol/L, respectively; p=0.02), and a significant correlation between preoperative serum HE4 levels and clinical risk categories was observed (rs= 0.385, p=0.014). The diagnostic performance of HE4 for risk categorization yielded a sensitivity of 70.83%, specificity of 81.25%, PPV of 77.27%, and NPV of 61.11%. For myometrial invasion prediction, HE4 demonstrated a sensitivity of 69.23%, specificity of 64.29%, PPV of 78.26%, NPV of 52.94%, and an accuracy of 67.50%. Conclusion: Serum HE4 levels display noteworthy sensitivity and specificity for both myometrial invasion and risk categorization in patients with endometrial cancer. This suggests that HE4 can be a valuable adjunct in predicting preoperative myometrial invasion and risk stratification in these patients.