Clinical significance of p53 protein expression and TP53 mutation status in colorectal cancer

Abstract In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the mutational status of TP53 . Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and mutational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between mutational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 mutation ( P < 0.001), TP53 mutation and higher N stage ( P = 0.024), and positive p53 expression and higher N stage ( P = 0.003). Positive p53 expression ( P = 0.018) was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift (p53 proportion, 0%) p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the mutational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with mutation status of TP53 and expression of p53 protein rather than mutation status of TP53 has more significant impact on the OS of CRC patients.