Humoral response to p53 is associated with conserved domains II and IV mutations in human colorectal cancer: A case-control study in Taiwan

To explore the relationship between mutations of the p53 gene, p53 protein accumulation in tumor tissues and the presence of anti-p53 antibodies (Ab) in sera, a matched case-control study with 63 colorectal cancer patients positive for p53-Ab was carried out. These control patients were matched for age, gender, as well as tumor site and stage with 63 colorectal cancer patients positive for p53-Ab. The study was designed to analyze their p53 gene mutations in exons 4-9 by the single strand conformation polymorphism (SSCP) followed by direct sequencing, as well as measuring p53 protein accumulation by immunohistochemistry. A significantly higher frequency of p53 mutations in exon 4-9 and positive immunohistochemical staining of p53 protein was observed in tumors from p53-Ab positive patients (55.56 and 84.13%, respectively) than in tumors from p53-Ab negative patients (22.22 and 60.32%, respectively). Using a conditional logistic regression model, the humoral response to p53 was found to be associated with p53 gene mutation (OR = 3.34; 95% CI, 1.31-8.54, p=0.012) and p53 protein accumulation (OR = 3.80; 95% CI, 1.02-14.14, p=0.047). Further analysis showed that the frequency of p53 mutations located in the conserved domains II (codons 112-141) and IV (codons 234-258) was significantly higher in p53-Ab positive patients than in p53-Ab negative patients (50.00% (16/32) vs. 8.33% (1/12), p=0.015, Fisher's exact test). Thus, our study demonstrated that the generation of p53 antibodies was usually correlated with the p53 protein accumulation and p53 gene mutation, especially mutations located in conserved domains II and IV.