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: p53 gene, p53 mutation, Anti-p53 auto-antibody, Cancer, Colorectal cancer

Core tip: Anti-p53 auto-antibodies are commonly produced in response to p53 mutations. Anti-p53 auto-antibody titres generally increase with tumour load, but not all patients who are initially sero-negative develop an auto-antibody response despite disease progression and metastases. Conversely, sero-positive patients do not lose their anti-p53 auto-antibodies despite the cancer being completely excised. In general, cancers with the highest p53 mutation rate, e.g., oesophageal and ovarian, demonstrate the highest anti-p53 auto-antibody rates; conversely, melanoma and testicular carcinoma with the lowest mutation rate have the lowest serum auto-antibody levels. Measurement of anti-p53 auto-antibodies may be useful in screening or monitoring for tumour recurrence.