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

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 wellas non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum humanepididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancersand comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benignovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses wascalculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patientswith ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levelssignificantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Usingbenign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off valuefor 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 sensitivityto 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 frombenign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinousepithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may providehigher accuracy for detecting epithelial ovarian cancer particularly in the early stages.