HE4 and Mesothelin: Novel Biomarkers of Ovarian Carcinoma in Patients with Pelvic Masses

Objectives: To evaluate the utility of novel serum tumor markers, HE4 and mesothelin either alone or incombination with CA125 in diagnosis and early detection of ovarian carcinoma in patients with pelvic masses.Subjects and methods: Sera were obtained preoperatively from 65 women underwent surgery for a pelvic massand 25 age- and menopausal status-matched healthy women. All samples were analyzed for levels of CA125,HE4, and mesothelin by serum based immunoassays and patients results were compared to final pathologyfindings.
Results: Of 65 patients with pelvic masses; 41 had histologically diagnosed ovarian cancer, and 24 hadbenign ovarian diseases. The studied tumor markers were significantly increased in malignant compared tobenign cases and healthy subjects, and in benign cases compared to healthy subjects (p<0.001). Based uponReceiver operator characteristic (ROC) curves analysis, HE4 had the highest sensitivity as a single marker indetecting ovarian malignancy (82.9%) and early stage malignancy (76.9%), followed by CA125, then mesothelin.The combination of HE4 and CA125 gave the highest sensitivity in detecting ovarian carcinoma and early stagedisease (90.2%, 84.6% respectively). Addition of mesothelin to this combination did not show any improvementin the sensitivity.
Conclusions: As a single marker, HE4 had the highest sensitivity for detecting ovarian carcinomaspecially early stage disease. Combined CA125 and HE4 was a more accurate predictor of ovarian malignancythan either alone.