Human Epididymis Protein 4 (HE4)

Human Epididymis Protein 4 (HE4) is a biomarker primarily used in the detection and monitoring of ovarian cancer, particularly epithelial ovarian cancer (EOC). It is a secreted glycoprotein that is overexpressed in ovarian cancer cells and can be measured in the blood.

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Key Features of HE4:

1. Tumor Marker for Ovarian Cancer – Elevated in epithelial ovarian cancer, especially serous and endometrioid subtypes.
2. More Specific than CA-125 – While CA-125 is also used in ovarian cancer detection, HE4 is less likely to be elevated in benign conditions (e.g., endometriosis, fibroids).
3. Used in Combination with CA-125 – The Risk of Ovarian Malignancy Algorithm (ROMA score) combines HE4 and CA-125 to assess ovarian cancer risk in premenopausal and postmenopausal women.
4. Can Be Used for Disease Monitoring – Helps track treatment response and recurrence in ovarian cancer patients.

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Clinical Uses of HE4 Testing:

✅ Ovarian Cancer Diagnosis & Risk Assessment

• HE4 is measured along with CA-125 to improve ovarian cancer detection.
• The ROMA Score (using HE4 + CA-125) stratifies women into low-risk or high-risk categories.

✅ Monitoring Treatment Response

• HE4 levels decrease with effective chemotherapy or surgery.

✅ Detecting Cancer Recurrence

• Rising HE4 levels may indicate early cancer relapse before imaging changes appear.

✅ Differentiating Malignant vs. Benign Pelvic Masses

• HE4 is less likely to be elevated in benign conditions compared to CA-125.

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HE4 vs. CA-125: Which is Better?

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Limitations of HE4 Testing:

❌ Not useful for all ovarian cancer types (e.g., mucinous tumors).
❌ Cannot replace imaging (Ultrasound, CT, MRI).
❌ Not a screening test for the general population—used mainly for high-risk individuals.

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Key Takeaways:

✔ HE4 is a biomarker for ovarian cancer, especially epithelial ovarian cancer.
✔ More specific than CA-125, reducing false positives from benign conditions.
✔ Used in risk assessment (ROMA Score), treatment monitoring, and recurrence detection.
✔ Should be interpreted with imaging and clinical findings for accurate diagnosis.