There is a current need to identify serum biomarkers that will aid in the early detection of Ovarian Cancer, as early detection results in significantly improved 5 year survival rates. We have identified potential diagnostic biomarkers through the analysis of gene arrays and key members of oncogenic pathways activated in most ovarian cancers. Human epididymis protein 4 (HE4) and Glycodelin were identified as two such candidates. They were evaluated by ELISA for the detection of ovarian cancer using serum panels from patients with ovarian epithelial cancer (OEC) and healthy controls. Monoclonal antibodies were generated in-house to recombinant HE4. Following pair selection, HRP-labeling of the detector antibody and ELISA optimization, an antigen sensitivity of 0.8ng/ml recombinant protein was achieved. 40 OEC sera (n=21 (Stage 2), n=7 (Stage 3), n=3 (Stage 4), n=9 (Stage unknown)) and 40 healthy controls were analyzed with the HE4 ELISA assay. Using a cutoff based on healthy control MEAN + 2SD, a specificity of 95% coupled with a sensitivity of 50% was achieved. For the Glycodelin studies, a commercial ELISA kit was used against a different 40 OEC sera panel (n=16 (Stage 2), n=15 (Stage 3), n=3 (Stage 4), n=6 (Stage unknown)) and 40 healthy controls. With this ELISA format, a specificity of 95% coupled with a sensitivity of 78% was achieved (healthy control MEAN + 2SD). When a panel of early Stage 1 OEC sera panel (n=19) was tested a specificity of 95 coupled with a sensitivity of 50% was achieved. These data indicate that HE4 and Glycodelin possess diagnostic utility in identifying ovarian cancer patients and substantiate efforts to further test these biomarkers in larger patient cohorts both individually and in combination with other markers.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]