Clinical utility of anti-p53 auto-antibody: systematic review and focus on colorectal cancer

Abstract

Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 auto-antibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses on the data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.

Keywords: Anti-p53 auto-antibody; Cancer; Colorectal cancer; p53 gene; p53 mutation.

Figure 1

Normal p53 function highlighted in green boxes and blue figures as described. Red boxes show mechanisms for inactivation; Normal p53 function highlighted in green and blue figures. PI3K: Phosphatidylinositol-3-kinase; PTEN: Phosphatase and tensin homolog; AKT: Protein kinase B; ATM: Ataxia telangiectasia mutated kinase; mTOR: Mammalian target of rapamycin; DAPK: Death-associated protein kinase; DRAM: Damage-regulated autophagy modulator; PUMA: p53-upregulated modulator of apoptosis; hTERT: Human telomerase reverse transcriptase.

Figure 2

Proposed mechanisms of anti-p53 auto-antibody induction. MHC: Major histocompatibility complex; CD8: Cluster of 8 differentiation; CTL: Cytotoxic T-cell; IL: Interleukin; APC: Antigen presenting cell.

Figure 3

Percent p53 mutations (International Agency for Research on Cancer, 2008) and percent anti-p53 auto-antibody incidence calculated in this review. r² = 0.45, Correlation = 0.59. CRC: Colorectal cancer; HCC: Hepatocellular carcinoma.