Correlations between p53-protein accumulation, serum antibodies and gene mutation in colorectal cancer

Abstract

Only half of colorectal‐cancer patients elicit serum antibodies in response to intratumoral p53‐gene mutations. Our study was designed to compare cellular events (p53‐protein accumulation and gene mutations) with the presence of circulating anti‐p53 antibodies (p53‐Ab). Thirty‐five colorectal‐cancer patients were studied for their intratumoral p53‐protein accumulation and circulating p53‐Ab. Tumour DNA was analyzed for genomic mutations in a sub‐set of 28 patients. In all, 18 tumours (51.4%) were positive by immunohistochemistry, and 17 tumour extracts were shown to contain “mutant” conformation p53 protein, 16 of them being were concordant by both methods. Of the 28 tumours tested by DGGE, 16 contained alterations in p53 exons 5 to 8 (57.1%). Of 12 tumours without detectable mutations, 10 were “mutant”‐conformation‐negative by immunohistochemistry and ELISA. Paradiploid tumors presented more frequently wild‐type p53 genes and were significantly less frequently immunohistochemistry‐ or p53‐Ab‐positive than polyploid tumors. Circulating p53‐Ab were detected in the serum of 11 patients (31%). In 9/11 cases, a gene mutation was found in the corresponding tumour. Three of four mutations in exon 8 and 3/3 mutations in exons 5‐6 were associated with p53‐Ab, in contrast with only 3/9 mutations in exon 7. We found good agreement in the detection of p53‐gene alterations by different methods. However, our data suggest that all gene mutations may not be equivalent in term of immunogenicity. Int. J. Cancer 81:712–718, 1999. © 1999 Wiley‐Liss, Inc.

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

“…21,22 In the current study, the proportion (13%) of seropositive patients is consistent with a previous report on CRC 15 but represents a lower figure than other studies reporting positivity rates varying from 18 to 32%. 16,18,20,[23][24][25] In a previous study, 26 we reported that Taiwan had the lowest frequency of p53 mutations (31%) and the highest frameshift mutation rates among various population studies, which agrees with half of the CRC patients with a p53 mutation in the tumor having circulating p53-Abs. 3 In accordance with other studies, 18,23,25-27 in our series, we found no correlation with demographic or clinicopathologic features, except for tumor location and nodal status of the tumor.…”

Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis

“…56 Over the years, these antibodies were shown to be found frequently in human cancer patients and to be associated mainly with TP53 missense mutations and accumulation of mutant protein in the tumor. 57,58 Such antibodies were found in the serum of patients with various types of cancer, including lung, 59,60 esophageal, 61,62 oral, 63 colorectal, 64 liver, 65 and more. p53-specific antibodies were also found in the M Monographs saliva of oral cancer patients.…”

Reevaluation of serum p53 antibody as a tumor marker in colorectal cancer patients

“…The half-life of mutant p53 protein in patient blood has been reported to be several hours, whereas that of wild-type p53 protein is only 20 min. The accumulation of p53 gene protein in the nuclei of malignant cells induces the production of serum antibody against p53 protein [5][6][7][8]. Thus, S-p53Ab as a serological marker of cancer has been the focus of much attention [9][10][11][12][13][14][15].…”