Abstract
BackgroundP53 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.MethodsSerum 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.ResultsTwenty-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.ConclusionsAnti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.
Highlights
P53 mutations are an adverse prognostic factor in esophageal cancer
The aim of this study was to investigate whether the level of serum anti-p53 and anti-KRas antibodies measured prior to CRT is a prognostic marker in esophageal carcinoma patients treated with CRT
This retrospective study is the first to evaluate the prognostic significance of anti-p53 and anti-KRas antibodies in esophageal carcinoma patients treated with CRT
Summary
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. The incidence of adenocarcinoma of the esophagus (ACE) increased 4-fold during this period in the United States, while that of squamous cell carcinoma (SCCE) declined by 30%. The risk factors, coexisting conditions, location in the esophagus, natural history and survival differ between these two histological subtypes. Despite these differences, therapeutic strategies are very similar and combine surgery, chemotherapy and radiotherapy [2]. Concomitant chemoradiation (CRT) is the standard treatment [3,4]
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