From the Guidelines
HE4 is not a reliable marker for uterine cancer and its levels do not typically increase with this condition. The primary use of HE4 is as a biomarker for ovarian cancer, where it often shows increased levels, particularly when used in conjunction with CA-125 [ 1 ]. In the context of uterine (endometrial) cancer, the focus is more on clinical examination, imaging studies such as transvaginal ultrasound, and histopathological examination of tissue samples obtained through endometrial biopsy. Key points to consider in the diagnosis of uterine cancer include:
- Clinical presentation and detailed history
- Transvaginal ultrasound for imaging
- Endometrial biopsy for histopathological examination
- CA-125 may be elevated in some cases, especially in advanced disease, but it lacks specificity and sensitivity for uterine cancer The use of HE4 in the diagnostic workup of uterine cancer is not supported by strong evidence, and its expression is more closely associated with epithelial cells of the reproductive tract, particularly the epididymis and fallopian tubes, rather than endometrial tissue [ 1 ]. Therefore, reliance on HE4 for screening or ruling out uterine cancer is not recommended. Instead, a comprehensive approach including clinical evaluation, imaging, and tissue diagnosis is preferred.
From the Research
HE4 Levels in Uterine Cancer
- HE4 levels have been found to be associated with uterine cancer, particularly endometrial cancer 2, 3.
- Increased serum HE4 levels may be associated with deeper myometrial invasion, extrauterine disease, and poorer prognosis in endometrial cancer patients 2.
- Serum HE4 levels were elevated in 85% of epithelial ovarian cancers (EOCs) and were most often elevated in women with high-grade serous and endometrioid EOCs 4.
Comparison with CA125
- HE4 has been found to be superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients 3.
- HE4 levels were more frequently elevated in patients with distant metastasis compared to local recurrences, and detected a recurrence with a median of 126 days earlier than clinical confirmation 3.
- The positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups 5.
Clinical Significance
- Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels 5.
- The high specificity of HE4 was superior in identifying benign ovarian disease, and optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03 pmol/L and 119.70 pmol/L before and after menopause, respectively 5.
- HE4 may be a useful biomarker in the management of endometrial cancer, particularly in identifying high-risk patients and detecting recurrent disease 2, 3.