Auto-antibody detection of ovarian cancer with paraneoplastic antigens.

Abstract

70 Background: The high mortality rate of ovarian cancer (OVCA) is due to late detection and high incidence of recurrence. Autoantibody diagnostic tests for early detection and prediction of recurrence have the potential to improve patient outcome. Paraneoplastic neurological syndromes (PNSs) are rare disorders due to remote effects of the immune response against a tumor, targeting both the tumor and healthy tissues such as muscle, brain, and nervous system. Symptoms of PNSs generally precede detection of a tumor; therefore paraneoplastic antibodies are a logical resource for the early detection of cancer. Two PNSs associated with OVCA are myositis and paraneoplastic cerebellar degeneration (PCD), which target muscle and purkinje cells, respectively. Our laboratory has detected the presence of several myositis and PCD associated paraneoplastic antibodies in the sera of patients with OVCA. Methods: Incubation of OVCA patient sera with commercially available paraneoplastic diagnostic line blots indicated presence of paraneoplastic antibodies. OVCA specific epitopes discovered previously in our laboratory by phage-display biopanning were evaluated for both homology to paraneoplastic antigens and for reactivity with PNS patient sera. Selected paraneoplastic antigens reactive with OVCA sera and OVCA specific epitopes homologous with paraneoplastic antigens or reactive with PNS patient sera were evaluated on western blot with OVCA sera, healthy control sera, and sera from patients with benign gynecological conditions. The sera screening will be replicated on ELISA. Recently identified paraneoplastic antigens associated with myositis and PCD that are expressed in OVCA tissue are being evaluated for reactivity with OVCA sera on western blot. Results: We have established a panel of four paraneoplastic antigens that in combination are able to discriminate OVCA sera from healthy patient sera and sera from patients with benign gynecological conditions. Conclusions: Although paraneoplastic syndromes are rare, paraneoplastic antibodies can be present in patients with ovarian cancer without PNS. A panel of paraneoplastic antigens for the autoantibody detection of ovarian cancer has the potential for development of a clinical test.