Evaluation of HE4 as an extrabiomarker to CA125 to improve detection of ovarian carcinoma: is it time for a step forward?

PURPOSE: To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma. METHODS: Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay. RESULTS: The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma. CONCLUSION: HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.

Methylation status of the gene promoter of cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancer.

OBJECTIVE: This study investigated the methylation status of the promoter of the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancer. DESIGN AND METHODS: CDKN2A methylation was quantified by real-time PCR in ovarian biopsies of 52 patients with ovarian cancer, 43 patients with benign ovarian tumors and 40 patients with benign uterine pathology and healthy ovaries. RESULTS: CDKN2A methylation was detected in the three groups. The methylation level was higher in the cancer patients than in the other two groups (p = 0.0003) but was not different between benign tumors and healthy ovarian tissue (p > 0.05). Using a cutoff threshold based on receiver-operating characteristic analysis, 21 patients with ovarian cancer and three patients with benign tumors were considered positive for CDKN2A methylation while all patients with healthy ovaries were considered negative. At the chosen cutoff, the diagnostic sensitivity was 40.4% and specificity 96.4%. CDKN2A methylation level and frequency were associated with high grade tumors (p = 0.0001 and p = 0.0005) but were not associated with disease stage or serum CA125 levels. However, it should be noted that most patients (92.3%) presented with advanced stage 3 or 4 disease. CONCLUSION: CDKN2A promoter methylation is common in ovarian cancer. Quantification of CDKN2A methylation may be useful in distinguishing malignant from benign ovarian tumors or healthy ovarian tissue.