title: Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass.
abstract: Serum autoantibodies against the p53 protein (p53 AAb) were analysed with a newly developed enzyme-linked immunosorbent assay (ELISA) based on highly purified and renatured p53. In a hospital-based cohort study, preoperative sera from 113 patients with ovarian cancer, 15 patients with borderline tumours and 117 patients with benign tumours of the ovaries were studied. The prevalence of p53 AAb in patients with invasive cancer was 19% (21/113). No p53 AAb were found in patients with borderline lesions or benign tumours. The ELISA had a specificity for malignancy of 99% (1 of 117; false-positive from a patient with severe diabetes mellitus) and a likelihood ratio (LR+) for a positive test result of 21.7 (elevated CA125 and malignancy: LR+ 3.7). p53 AAb were only detectable in patients with immunohistochemical staining of nuclear p53 in the tumour (P = 0.006). Presence of p53 AAb positively correlated with tumour stage (P = 0.034) and grade (P = 0.009). Kaplan-Meier analysis showed both a shortened overall survival (P = 0.0016, log-rank) and relapse-free survival (P = 0.055) for p53 AAb-positive patients (median follow-up 22 months). High titres related to even worse prognosis. p53 AAb independently related to poor survival adjusting for stage (P = 0.026), grade (P = 0.029) and residual disease after surgery (P = 0.005). Preoperative findings of adnexal mass with serum p53 AAb are strongly suggestive of an aggressive invasive ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Ulm, Ulm, 89075, Germany.
authors.forename: F D
authors.initials: FD
authors.lastname: Vogl
authors.forename: M
authors.initials: M
authors.lastname: Frey
authors.forename: R
authors.initials: R
authors.lastname: Kreienberg
authors.forename: I B
authors.initials: IB
authors.lastname: Runnebaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D015331:Cohort Studies; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53