title: Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy.
abstract: BACKGROUND
  P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma.
  
  
  METHODS
  Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted.
  
  
  RESULTS
  Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT.
  
  
  CONCLUSIONS
  Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.
authors.affiliation: Radiation Oncology Department, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.forename: Laurent
authors.initials: L
authors.lastname: Quero
authors.forename: Vincent
authors.initials: V
authors.lastname: Pacault
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Schlageter
authors.forename: Valerie
authors.initials: V
authors.lastname: Baruch-Hennequin
authors.forename: Christophe
authors.initials: C
authors.lastname: Hennequin
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000628:therapy; D059248:Chemoradiotherapy; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*; D018631:ras Proteins / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins