Humoral response to P53 in human colorectal tumors: A prospective study of1,209 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 durin g colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Usin g a quantitative enzyme-linked immunosorbent assay, we analyzed serum sampl es from 998 CRC patients and from 211 patients with polyp. Levels of p53-Ab s were defined as negative (<10 U/<mu>L), low (10-76 U/muL) and high (>76 U /muL). Overall, 13.0% of CRC patients and less than 1% of polyp patients ha d increased serum p53-Ab levels. High p53-Ab levels were only seen in patie nts with invasive carcinomas. The parameters that were significantly and in dependently 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% Cl, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% Cl , 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 sig nificant effect disappeared in a Cox regression model adjusting for sex, ag e, tumor location, carcinoembryonic antigen levels, gross findings, histolo gic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and in crease with advanced node metastasis. Furthermore, the seemingly adverse ef fect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors. (C) 2001 Wiley-Liss, Inc.