Diagnostic Performance of Serum Human Epididymis Protein 4 (HE4) for Prediction of Malignancy in Ovarian Masses

Document Type : Research Articles


1 Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, Ansari Nagar, New Delhi, India.

2 Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, New Delhi, India.

3 Department of Research, National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh India.


Background: Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction.
This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as well
as non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum human
epididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancers
and comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benign
ovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125
levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses was
calculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patients
with ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levels
significantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Using
benign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off value
for diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6%
vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivity
to detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125
(92.61% vs. 63.41%). Conclusion: Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer from
benign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinous
epithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may provide
higher accuracy for detecting epithelial ovarian cancer particularly in the early stages.


Main Subjects