Development and evaluation of Keratin 7/19 serum test for ovarian cancer in combination with biomarkers CA125 and HE4

Abstract

Ovarian neoplasms are one of the most common pathologies among women of all age groups. It has been estimated that up to 10% of all women in the United States will undergo a surgical procedure owing to a suspected ovarian mass during their lifetime, and around a fifth of these women will suffer from malignancy. Early detection of ovarian cancer is crucial for successful treatment and survival. The aim of this master thesis was to develop a Keratin 7/19 serum test for ovarian cancer which in combination with already established biomarkers CA125 and HE4 could increase the sensitivity of cancer detection while maintaining high specificity. Different antibody combinations directed against keratin 7/19 were evaluated as possible candidates for an ovarian cancer serum test based on a “sandwich” type enzyme immunoassay. The combination K7A/K19A showed promising results and was optimized as a keratin7/19 serum test with sufficient technical performance allowing clinical valuation on patient serum samples. The clinical evaluation showed that the test exhibited a surprisingly high specificity and a high discrimination power in distinguishing between benign disease and cancer. Only low concentrations of keratin 7/19 were detected in both benign disease samples and blood donor samples. The test exhibited high sensitivity for ovarian cancer and could possibly be used as a complement to the already established tumor markers CA125 and HE4. However, further evaluation is needed on a larger ovarian cancer population with clear classified tumor grade and stage. Analysis of other types of cancers and benign diseases indicate that additional clinical applications may exist for the test. Obtained results encourage for further studies in bladder cancer.