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. 2010 Mar;19(3):859-68.
doi: 10.1158/1055-9965.EPI-09-0880. Epub 2010 Mar 3.

p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer

Karen S Anderson  1 , Jessica Wong, Allison Vitonis, Christopher P Crum, Patrick M Sluss, Joshua Labaer, Daniel Cramer
Affiliations

p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer

Karen S Anderson et al. Cancer Epidemiol Biomarkers Prev. 2010 Mar.

Abstract

Background: This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer.

Methods: p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival.

Results: p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer.

Conclusions: Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer.

Impact: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.

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Figures

Figure 1
Figure 1. p53 autoantibodies are highly specific biomarkers in serous ovarian cancer
A. Sera derived from 30 ovarian cancer patients and 30 age-matched healthy women were tested for p53-specific antibodies by RAPID ELISA. The cut-off value (mean signal + 2 S.D. of the controls) is shown as a dotted line (13.1 × 106). B. Distribution of p53 autoantibodies in serous cases and controls. The signal intensity for serous cases (n=60) and all controls (n=120) are shown as a percentage of the total sera. The distribution of p53-AAb signal intensity for controls (open bars) is a unimodal distribution and the cases show a bimodal distribution (filled bars).
Figure 1
Figure 1. p53 autoantibodies are highly specific biomarkers in serous ovarian cancer
A. Sera derived from 30 ovarian cancer patients and 30 age-matched healthy women were tested for p53-specific antibodies by RAPID ELISA. The cut-off value (mean signal + 2 S.D. of the controls) is shown as a dotted line (13.1 × 106). B. Distribution of p53 autoantibodies in serous cases and controls. The signal intensity for serous cases (n=60) and all controls (n=120) are shown as a percentage of the total sera. The distribution of p53-AAb signal intensity for controls (open bars) is a unimodal distribution and the cases show a bimodal distribution (filled bars).
Figure 2
Figure 2. Comparison of ROC curves of p53 autoantibodies, CA 125, and HE4
A. Sera derived from 60 serous ovarian cancer patients and 90 age-matched healthy women were tested for CA 125 (blue), HE4 (red), and p53-specific antibodies (green), and ROC curves were calculated. The combination of all three biomarkers is shown in orange. B. Sera derived from 60 serous ovarian cancer patients and 30 women with benign ovarian disease were tested for CA 125 (blue), HE4 (red), and p53-specific antibodies (green), and ROC curves were calculated.
Figure 2
Figure 2. Comparison of ROC curves of p53 autoantibodies, CA 125, and HE4
A. Sera derived from 60 serous ovarian cancer patients and 90 age-matched healthy women were tested for CA 125 (blue), HE4 (red), and p53-specific antibodies (green), and ROC curves were calculated. The combination of all three biomarkers is shown in orange. B. Sera derived from 60 serous ovarian cancer patients and 30 women with benign ovarian disease were tested for CA 125 (blue), HE4 (red), and p53-specific antibodies (green), and ROC curves were calculated.
Figure 3
Figure 3. Overall survival is increased in patients with p53 antibodies
Kaplan-Meier curves comparing overall survival between p53 antibody-positive (red) and antibody-negative (blue) patients.
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