Predictive Role of HE4 in Diagnosis of Ovarian Tumors

Approximately 20% of women develop an ovarian cyst or pelvic mass at some point in their lives. Due to high false positivity of CA-125, women with various benign ovarian tumors simulating malignant masses undergo extensive debulking surgery resulting in increased morbidity. Serum HE4 is a useful test for better discrimination of benign or malignant nature of pelvic masses in preoperative period. Our study gives an update on the biological markers specifically CA-125 and a novel tumor marker HE4 and aims to reduce the debulking surgeries done for benign pathology.

The total study population (n = 302) included women who were operated with suspicious ovarian malignant mass (n = 238) with benign (n = 98), borderline (n = 6), and malignant (n = 134) ovarian tumors. Cutoff of CA-125 was 35 U/mL, and for HE4 140 pM for postmenopausal and 70 pM for premenopausal women were calculated at 86% and 81% accuracy, respectively. Statistical analysis was done using SPSS version 20.

The cutoff values of CA-125 were able to differentiate between benign, borderline, and malignant tumors with statistical significance (p < 0.05), whereas the cutoff values of HE4 significantly (p < 0.05) differentiated benign tumors from the malignant tumors, but not from the borderline tumors. Serum CA-125 has significantly higher sensitivity and NPV (95%, 72%, respectively) compared to HE4 (81%, 52%) and combined HE4 plus CA-125 (84%, 59%), whereas specificity, PPV, and AUC were higher for combined CA-125 plus HE4 (93%, 98%, 90%, respectively) compared to HE4 (83%, 95%, 88%) and CA-125 (48%, 88%, 87%).

Measuring serum HE4 along with CA-125 in preoperative diagnosis helps in excluding benign ovarian tumors in which CA-125 was falsely raised, especially in center where frozen section is not available, thus potentially decreasing morbid debulking surgeries done for benign ovarian tumors.