Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.