Abstract
9725 Background: The purpose of this study was to evaluate the clinical impact of p53 antibodies, suggested to be associated with advanced tumor state and poor survival rate. Methods: We analyzed the frequency of circulating anti-p53 antibodies, levels of free p53 protein, and concentration of CEA in sera of colorectal cancer patients (n=48, ELISA) as well as expression of p53/CEA in the tumor (immunohistology) and correlated with the UICC stage. Results: 39.6% of all tested patients (n=19/48) expressed wild-type (wt) p53-specific-IgG-antibodies: 26% in UICC I (n=5/19), 16% in UICC II (n=3/19), 21% in UICC III (n=4/19), and 37% in UICC IV (n=7/19). 31.3% (n=15/48) showed a negative response to p53 and 29.2% (n=14/48) were within the critical range. In addition, similar levels of p53-IgG1/IgG2-subtypes were observed in patients with p53 antibodies (ELISA). No correlation was found between levels of free p53 protein and antibody levels. Immunohistologically 62.5% of the tumors (n=10/16) overexpressed p53 (clone DO-7) independent of UICC stage. The presence of wt p53-IgG-antibodies was correlated with strong p53 staining within the tumor. In addition, 29.2% (n=14/48) of the patients expressed high CEA levels depending on their UICC stage (n=0/6 UICC I, n=0/12 UICC II, n=2/9 UICC III, and n=12/21 UICC IV, ELISA). CEA expression within the tumor and UICC stage was strongly correlated (75%, n=12/16). Five different point mutations at 5 different positions of wt p53 sequence (4 in DNA-binding core domain) were observed in tumors (n=16, RT-PCR), indicating no association with the p53 humoral response and UICC stage. Conclusions: This study suggests that a humoral response to p53 is strongly correlated with intracellular accumulation of p53 within the tumor but independent from free p53 protein serum levels and p53 gene mutations. In contrast to CEA, presence of p53 auto-antibodies is not correlated with UICC stage. p53 auto-antibodies seem not to be predictive in poor outcome and irrelevant in colorectal cancer diagnosis. No significant financial relationships to disclose.
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