Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy

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.

Concordance of studies for nodal staging is prognostic for worse survival in esophageal cancer

“…There are many factors that may be prognostic for overall survival in esophageal cancer. Tumor grade, growth patterns, sex, molecular markers, and stage are among a few that are believed to be important . The nodal status at the time of diagnosis can be particularly significant for determining treatment strategy, as well as prognosticating survival .…”

“…Tumor grade, growth patterns, sex, molecular markers, and stage are among a few that are believed to be important. [2][3][4][5][6] The nodal status at the time of diagnosis can be particularly significant for determining treatment strategy, as well as prognosticating survival. 7,8 However, the currently utilized methods to evaluate nodal status are limited by their accuracy.…”

p53 molecular approach to diagnosis and treatment of esophageal squamous cell carcinoma

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Harnessing the immune system to provide long-term survival in patients with melanoma and other solid tumors

“…However, median OS is a snapshot comparison of a single time point and thus provides a limited measure of benefit. In particular, differences in the durability of survival, i.e., information on those patients that may survive longer than the median value, are not conveyed 56 , 57 . Additionally, log-rank tests are used to determine if the difference observed between 2 survival curves at a certain time point is statistically significant.…”