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Elevation of TP53 autoantibody before CA125 in preclinical invasive epithelial ovarian cancer

Abstract

Purpose: The TP53 tumor-suppressor gene is mutated in >95% of high-grade serous ovarian cancers. Detecting an autologous antibody response to TP53 that might improve early detection.Experimental Design: An immunoassay was developed to measure TP53 autoantibody in sera from 378 cases of invasive epithelial ovarian cancer and 944 age-matched healthy controls from the United States, Australia, and the United Kingdom. Serial preclinical samples from cases and controls were also assayed from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).Results: Using a cutoff value of 78 U/mL to achieve a specificity of 97.4%, TP53 autoantibody was elevated in 30% of 50 cases from MD Anderson, 21.3% of 108 cases from the Australian Ovarian Cancer Study, and 21% of 220 cases from the UKCTOCS. Among 164 cases with rising CA125 detected with the UKCTOCS risk of ovarian cancer algorithm (ROCA), 20.7% had elevated TP53 autoantibody. In cases missed by the ROCA, 16% of cases had elevated TP53 autoantibody. Of the 34 ovarian cancer cases detected with the ROCA, TP53 autoantibody titers were elevated 11.0 months before CA125. In the 9 cases missed by the ROCA, TP53 autoantibody was elevated 22.9 months before cancer diagnosis. Similar sensitivity was obtained using assays with specific mutant and wild-type TP53.Conclusions: TP53 autoantibody levels provide a biomarker with clinically significant lead time over elevation of CA125 or an elevated ROCA value. Quantitative assessment of autoantibodies in combination with CA125 holds promise for earlier detection of invasive epithelial ovarian cancer. Clin Cancer Res; 23(19); 5912-22. (c)2017 AACR.

Type Journal
ISBN 1078-0432 (Print) 1078-0432 (Linking)
Authors Yang, W. L.; Gentry-Maharaj, A.; Simmons, A.; Ryan, A.; Fourkala, E. O.; Lu, Z.; Baggerly, K. A.; Zhao, Y.; Lu, K. H.; Bowtell, D.; Jacobs, I.; Skates, S. J.; He, W. W.; Menon, U.; Bast, R. C., Jr.; Group, Aocs Study
Responsible Garvan Author
Publisher Name CLINICAL CANCER RESEARCH
Published Date 2017-10-01
Published Volume 23
Published Issue 19
Published Pages 5912-5922
Status Published in-print
DOI 10.1158/1078-0432.CCR-17-0284
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28637689