Abstract 2838: TP53 autoantibody can detect CA125 screen negative ovarian cancer cases and can be elevated prior to CA125 in preclinical ovarian cancer
Authors: Yang Wei-Lei , Simmons Archana , Lu Zhen , Baggerly Keith , Lu Karen , Gentry-Maharaj Alex , Menon Usha , Jacobs Ian , Bast Robert C. 
Published: August 2015

Abstract
Detection of ovarian cancer in early stage could improve mortality from the disease by 10-30%. Most attempts to utilize serum biomarkers for early detection of ovarian cancer have focused on CA125. As CA125 is expressed by only 80% of ovarian cancers, multiple biomarkers will be required to detect ovarian cancers that fail to express the antigen. In studies with preclinical samples to date, no biomarker has been consistently elevated prior to CA125. Detecting an autologous immune response to tumor associated antigens might provide improved lead time. TP53 is mutated and overexpressed in virtually all high grade serous ovarian cancers. Autoantibodies reactive with wtTP53 have been reported in approximately 15% of ovarian cancers at the time of conventional diagnosis, but most reports have studied a limited number of cases and preclinical sera have not previously been tested.
We have developed a novel immunoassay for quantitating TP53-specific autoantibody (AAb) in small volumes (2 uL) of serum. Samples from the MD Anderson Cancer Center Tissue Bank (MDACC), the MDACC Ovarian SPORE NROS screening study, the Australian Ovarian Cancer Study (AOCS) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) were used for discovery and validation. Assay cut-offs were determined by including less than 2% false positive samples in each control group (98% specificity of the assay).
Elevated titers of TP53 AAb were detected in 13 of 50 sera (26%) from MDACC patients with stage III-IV ovarian cancer and in 4 of 216 sera (1.9%) from healthy controls from the NROS study. Using the same cut-off we detected TP53 AAb in 28 of 108 cases (25.9%), 7 of 109 benign controls (6.4%) and 10 of 464 normal controls (2.1%) from the AOCS study. TP53 AAb was found in 3 of 12 cases (25.0%) in early stage (I/II) and 22 of 90 cases (24.4%) in late stage (III/IV). To further validate the result in the AOCS, we analyzed 2,471 serial serum samples from the UKCTOCS trial. Elevated TP53 AAb was found in 18 of 87 cases (20.7%) and 8 of 435 normal controls (1.8%). Increased titers were detected in 6 of 32 cases (18.8%) in early stage and 12 of 55 cases (21.8%) in late stage. Positivity was found in 11 of 49 cases (22.5%) detected with rising CA125 and 7 of 38 (18.4%) cases not detected with rising CA125. TP53 AAb titers rose prior to CA125 in 7 of 11 cases (63.6%). In 11 TP53 AAb (+) and CA125 (-) cases, TP53 AAb titers rose a mean of 13.5 months and a median of 5 months prior to CA125. In 7 TP53 AAb (+) and CA125 (-) cases, titers rose a mean of 33 months and a median of 29 months prior to cancer diagnosis. Consequently, quantitative assessment of TP53 AAb titers holds promise for earlier detection of ovarian cancer in combination with CA125.
Citation Format: Wei-Lei Yang, Archana Simmons, Zhen Lu, Keith Baggerly, Karen Lu, Alex Gentry-Maharaj, Usha Menon, Ian Jacobs, Robert C. Bast. TP53 autoantibody can detect CA125 screen negative ovarian cancer cases and can be elevated prior to CA125 in preclinical ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2838. doi:10.1158/1538-7445.AM2015-2838