Auto-antibodies against P53—a useful complementary biomarker for ovarian cancer screening?

More than 60% of ovarian cancers are diagnosed in late stage, when 5-year survival is less than 30%. Cases diagnosed at early stage have markedly better survival outcomes (1), and this survival difference has prompted extensive research on methods for early detection and ovarian cancer screening. Current strategies for earlierstage detection of ovarian cancer use a combination of blood-based biomarkers and trans-vaginal ultrasound (TVUS) imaging. To date, the best available biomarker for ovarian cancer is ovarian tumor-associated antigen CA125; however, CA125 demonstrates limited sensitivity for early stage disease. While the vast majority (~80%) of ovarian tumors express CA125, only 50–60% of women with early stage cancers have elevated circulating CA125 levels (concentrations >35 U/mL) at presentation, possibly because small tumors may not shed sufficient amounts of CA125 into the circulation (2). In prospective studies using prediagnosis samples, we (3) and others (4,5) have found that CA125 provides good diagnostic discrimination for ovarian cancer only when blood samples had been taken relatively shortly (≤6 months) before diagnosis, and that it mostly detected tumors that were clinically advanced at the time of diagnosis. Similar observations were made for human epididymis protein 4 (HE4), the second best available ovarian cancer marker to date (3-5). In screening trials, the combination of CA125 with TVUS provided either no reduction in ovarian cancer mortality [Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), USA] (6), or only a modest and marginally significant reduction when using an algorithm (“Risk of Ovarian Cancer”, ROCA) based on serial CA125 measurements [United Kingdom Collaborative Trial on Ovarian Cancer Screening (UKCTOCS)] (7). Although the prospective ROCA algorithm clearly improves sensitivity of screening by CA125, a substantial proportion of ovarian cancer cases remain undetected by this method, underscoring the need for complementary and more sensitive biomarkers for the detection of earlier-stage ovarian cancer.