title: The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival.
abstract: BACKGROUND
  Lung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis.
  
  
  METHODS
  Serum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983-1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany).
  
  
  RESULTS
  The present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 - 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets. Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to death.
  
  
  CONCLUSIONS
  The result of the present retrospective study indicates that anti-p53 antibodies are not suitable for predictions concerning selection of patients with a more favourable outcome. Further prospective studies are, though, needed to fully elucidate this issue.
authors.affiliation: Department of Oncology, University Hospital, 751 85 Uppsala, Sweden. Michael.Bergqvist@onkologi.uu.se
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Daniel
authors.initials: D
authors.lastname: Brattström
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Patrik
authors.initials: P
authors.lastname: Hesselius
authors.forename: Ola
authors.initials: O
authors.lastname: Brodin
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wagenius
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D000906:Antibodies / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D000906:Antibodies; D016159:Tumor Suppressor Protein p53