[Immunotyping- and characterisation of p53 autoantibodies in serums of mamma carcinoma patients in Syria during and after chemo- and radio therapy]

ABSTRACT

Carcinogenesis is a multistage process, involving oncogenes activation and tumor suppressor genes inactivation, as well as complex interactions between tumor and host tissues, leading ultimately to an invasive metastatic phenotype. p53 plays a critical role in tumor suppression mainly by inducing growth arrest, apoptosis, and senescence, as well as by blocking angiogenesis. In addition, p53 generally confers the cancer cell sensitivity to chemoradiation. Thus, p53 becomes the most appealing target for mechanism-driven anticancer therapy. For more than 30 years it has been known that cancer patients develop antibodies against p53. Many reports showed a very high frequency of p53 autoantibody positivity in the sera of patients with mamma carcinoma. This observation appointed the hopes of using p53 autoantibodies for diagnosis and prognosis. In addition there was a controversy whether p53 autoantibodies correlate with a good or bad prognosis. The reason for this controversy may be the use of different methods for the detection of p53 autoantibodies. Therefore, in this study, sera from mama carcinoma patients were initially tested by two different methods namely ELISA and Western Blot. In addition to the ELISA and Western Blot-analyses, we developed a filter binding epitopes, which are recognized by p53 autoantibodies. This assay allowed the mapping of the epitopes, which are recognized by p53 autoantibodies. The sequences of these epitopes might be useful for the treatment of tumor patients either by neutralizing p53 autoantibodies or for vaccination. Common epitopes are located in regions on the polypeptide chain of p53, which are functionally important for the role of p53 in growth control. Thus, the knowledge of these epitopes might be useful for the development of new strategies for cancer therapy