Departments of Pathology, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, and Research Institute for Endocrine Sciences, San 2-20 Keumam-Dong Dukjin-gu, Jeonju, 54907, Republic of Korea.
Department of Surgery, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University, and Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.
BMC Cancer. 2022 Aug 31;22(1):940. doi: 10.1186/s12885-022-10039-y.
In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational 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 variational 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 variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 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 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.
在人类结直肠癌(CRC)中,TP53 是最重要的驱动基因之一。免疫组织化学(IHC)最常用于评估 TP53 的变异状态。最近,TP53 基因的下一代测序(NGS)有所增加。然而,据我们所知,尚未研究通过 IHC 和 NGS 评估的 TP53 状态之间的比较。因此,本研究的主要目的是比较通过 IHC 和 NGS 评估的 CRC 患者的 TP53 状态的临床效果。次要目的是研究 IHC 中 p53 的表达与 NGS 中 TP53 变异状态之间的相关性。我们对 204 例 CRC 人类样本进行了 p53 的免疫组织化学染色和 NGS 的 TP53 测序。然后,我们分析了 TP53 变异状态与 p53 表达之间的相关性,以及它们在 CRC 患者中的预后影响。p53 表达与 TP53 变异、TP53 变异与较高的 N 分期以及阳性 p53 表达与较高的 N 分期之间存在显著相关性。p53 的阳性 IHC 表达通过单因素分析与 CRC 患者的总生存(OS)显著相关,并通过多因素分析显示为独立的预后因素。此外,无意义/移码 p53 表达模式的预后明显好于野生型和错义 p53 表达模式。然而,TP53 的变异状态在 CRC 患者的 OS 中并不显著。这些结果表明,p53 蛋白的 IHC 表达与 TP53 的变异状态和 p53 蛋白的表达相关,而不是 TP53 的变异状态对 CRC 患者的 OS 有更显著的影响。