p53 autoantibodies, cytokine levels and ovarian carcinogenesis

Objective: To address the hypothesis that type II ovarian carcinoma, mutation of p53 and plasma levels of particular cytokines are associated with the generation of p53-specific serum autoantibody (AAb) responses in patients. Methods: Levels of CA125, 17 cytokines and AAbs to tumor-associated antigens including p53 were measured in plasma of 130 gynecologic tumor patients and 84 healthy controls. TP53 exons 4-9 were sequenced in tumor specimens. Results: p53 AAbs are associated with high grade, but not low grade ovarian carcinoma. Seropositivity for p53 AAb occurred only in those ovarian carcinoma patients whose tumors contained mutated TP53, regardless of the exon targeted. Higher p53 AAb levels were detected in ovarian carcinoma patients who had higher stage disease, but p53 AAb levels were not correlated with CA125 levels. Among high-grade carcinoma patients, there was no relationship between p53 AAb seropositivity and seropositivity to other tumor-associated antigens tested, CA125 level or survival outcome. Both high and low grade ovarian carcinoma patients exhibited elevated levels of IL6, IL8 and IL10 as compared to healthy volunteers, although increased levels of IL5, MCP1, MIP1 and TNFα were associated only with high grade and advanced disease. Higher levels of p53AAb responses were correlated with elevated circulating IL4 and IL12, but reduced IL8 levels. Conclusion: Type II, but not type I, ovarian carcinoma patients had elevated serum levels of p53 AAb. P53 AAb is associated with mutation of TP53, higher plasma IL4 and IL12 but lower plasma IL8 levels and no survival advantage.