Esophageal cancer is a public health issue worldwide. Its incidence has remained stable over the past thirty years but its pathologic features have changed dramatically. 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%. In contrast, the incidence of SCCE is highest in Asia, southern and eastern Africa, and northern France, with an annual mortality rate approximating 100 per 100,000 . The risk factors, coexisting conditions, location in the esophagus, natural history and survival differ between these two histological subtypes. Yet despite these differences, therapeutic strategies are very similar and combine surgery, chemotherapy and radiotherapy . In locally advanced disease, concomitant chemoradiation (CRT) is the standard treatment [3, 4].
Major prognostic factors for esophageal carcinomas include clinical factors (general condition, initial weight loss, baseline hemoglobin level), factors related to local spread (TNM stage , lymph node micrometastases, the ratio between involved and sampled nodes, extracapsular lymph node involvement), and factors related to the radicality of surgery or to response to medical treatment evaluated radiographically or endoscopically. These factors were recently reviewed for ACE . In addition, molecular pathology has revealed numerous genes and molecules associated with tumor invasion and metastasis, some of which exert a prognostic impact per se. A better knowledge of these factors may not only improve prognostication but may offer new individually tailored therapeutic options .
Esophageal carcinogenesis is a multi-step process that transforms normal human cells into tumor cells following multiple genetic alterations. The circumvention of apoptosis appears to play an early and central role in this process. Mutations of the p53 gene are responsible for reduced chemo- and radio-induced apoptosis in esophageal cancer . These mutations are present in around 50% of esophageal cancers, and associated with advanced-stage disease, poor response to CRT and shorter survival [9, 10]. It has even been suggested that the analysis of p53 polymorphisms performed on endoscopic biopsies could identify patients with Barrett's esophagus who are at risk of neoplastic progression. It could therefore complement the histological examination in deciding the frequency of endoscopic surveillance in this population.
KRas is a membrane-bound guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-binding (G) protein that serves as a "molecular switch," converting signals from the cell membrane to the nucleus. These chemical signals lead to protein synthesis and the regulation of cell survival, proliferation, and differentiation. It is mutated in 30% of solid tumors, and particularly in 95% of pancreatic cancers and 50% of colon cancer, but probably only in less than 10% of esophageal tumors . However, some reports have suggested much higher levels of mutations in esophageal carcinomas. In colon cancer, Ras mutations have been shown to be predictive of resistance to anti-EGFR therapy .
Gene mutations lead to the synthesis and accumulation of physically altered proteins that are recognized as « non-self ». The immune system develops antibodies directed against these aberrant proteins. The detection of serum antibodies specific for p53 or KRas could be an easy way to determine an individual's mutational status. 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.