title: P53 autoantibodies in sera from Danish ovarian cancer patients and their correlation with clinical data and prognosis.
abstract: The p53 gene, a tumour suppressor gene located on the short arm of chromosome 17 (17p13), is frequently mutated in various human tumours. Accumulation of p53 protein in neoplastic cells and its release following tumour necrosis can lead to development of circulating autoantibodies (AAb) against p53. Earlier studies of ovarian cancer (OC) patients reported different frequencies of p53 AAb and conclusions regarding the clinical and prognostic value of these AAb have not been in agreement. We therefore analysed for the presence of p53 AAb in a total of 227 preoperative serum samples from 193 OC patients and 34 patients with ovarian borderline tumours, and, in addition, serum samples from 86 healthy controls. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum IgG antibodies against p53. The p53 protein used in the assay was produced as a hexahistidine-tagged fusion protein by baculovirus-infected Spodoptera frugiperda cells. Cut-off values for p53 AAb were evaluated, and correlations of p53 AAb with clinical-, biochemical data and survival were examined. We found a low sensitivity for p53 AAb alone, and no major additional effect of the detection rate of CA125 was found. No significant associations were found between p53 AAb and clinical stage, age, histological subtype and radicality after primary surgery. In contrast, we found significantly elevated CA125 levels in p53 AAb-positive patients compared to lower CA125 levels in p53 AAb-negative patients (p=0.003). No significant differences were found between p53 AAb-positive and p53 AAb-negative patients in the univariate and multivariate survival analyses. In conclusion, in a screening study for OC serum p53 AAb levels are of no diagnostic value, even if combined with the tumour marker CA125. The presence of increased serum p53 AAb in patients with diagnosed OC could not be correlated with any clinical data and preoperative serum p53 AAb status had no evident value.
authors.affiliation: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. estrid@cancer.dk
authors.forename: Estrid V S
authors.initials: EV
authors.lastname: Høgdall
authors.forename: Claus K
authors.initials: CK
authors.lastname: Høgdall
authors.forename: Jan
authors.initials: J
authors.lastname: Blaakaer
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Eva
authors.initials: E
authors.lastname: Glud
authors.forename: Lise
authors.initials: L
authors.lastname: Christensen
authors.forename: Johannes E
authors.initials: JE
authors.lastname: Bock
authors.forename: Bent
authors.initials: B
authors.lastname: Nørgaard-Pedersen
authors.forename: Allan
authors.initials: A
authors.lastname: Wiik
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D018394:CA-125 Antigen / Q000097:blood; D003718:Denmark; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D011994:Recombinant Proteins / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D018394:CA-125 Antigen; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53