Antibody Immunity to the p53 Oncogenic Protein Is a Prognostic Indicator in Ovarian Cancer

Abstract

Presence of intratumoral T-cell infiltration has been linked to improved survival in ovarian cancer patients. We questioned whether antibody immunity specific for ovarian cancer tumor antigens would predict disease outcome. We evaluated humoral immune responses against ovarian cancer antigens p53, HER-2/neu, and topoisomerase IIα. Serum was collected from 104 women (median age, 59 years; range, 34 to 89 years) at the time of their initial definitive surgery for ovarian cancer. Serum was analyzed by enzyme-linked immunosorbent assay for antibodies to p53, HER-2/neu, and topoisomerase IIα proteins. Antibody immunity to tetanus toxoid was assessed as a control. The incidence of humoral immunity at the time of diagnosis to any of these three antigens was tabulated. For patients with advanced-stage disease (III/IV), correlation was made between the presence of tumor-specific immunity at the time of diagnosis and overall survival. Patients were followed for a median of 1.8 years. Multivariate analysis showed the presence of p53 antibodies to be an independent variable for prediction of overall survival in advanced-stage patients. Overall survival was significantly higher for patients with antibodies to p53 when compared with patients without p53 antibodies (P = .01). The median survival for p53 antibody-positive patients was 51 months (95% CI, 23.5 to 60.5 months) compared with 24 months (95% CI, 19.4 to 28.6 months) for patients without antibodies to p53. Data presented here demonstrate that advanced stage ovarian cancer patients can have detectable tumor-specific antibody immunity and that immunity to p53 may predict improved overall survival in patients with advanced-stage disease.