Clinical significance of p53 protein expression and TP53 variation 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 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.

CD10 Expression Correlates with Earlier Tumour Stages and Left-Sided Tumour Location in Colorectal Cancer but Has No Prognostic Impact in a European Cohort

“…Further correlations with histopathological features in the CRC cohort suggest associations of CD10 expression with aggressive CRC phenotypes, i.e., p53 positivity, which indicates accumulation of p53 mutations, as mutant p53 is more stable and, therefore, accessible for immunohistochemical staining [29], and nuclear β-catenin expression. p53 mutations are among the most common genetic alterations found in human tumours and are detected in up to 43% of CRCs.…”

“…Mutations in the Wnt/β-catenin pathway, which are also common in sporadic CRC, stabilize β-catenin, allowing its accumulation and translocation to the nucleus, where it acts as an activating transcription factor involved in cell proliferation and transmission [31]. Both, p53 and nuclear β-catenin are associated with tumour progression in sporadic CRC and are negative prognostic factors for disease-free and overall survival in CRC [29,32]. As previous studies and our data demonstrate, CD10 is expressed in early CRC carcinogenesis [21,22,24] and disappears in the more advanced tumour stages.…”

Evaluating the role of wound‐healing genes in conjunction with stool routine and serum tumor markers for colorectal cancer diagnosis and prognostic implications

“…However, the specific studies on the relation of the biomarker and wound‐healing genes in CRC are still not explicitly studied; the wound‐healing genes are reported to play a role in CRC progression and proliferation. 35 , 36 , 37 , 38 , 39 …”

Resistin-like beta reduction is associated to low survival rate and is downregulated by adjuvant therapy in colorectal cancer patients

“…In particular, the expression levels of RETNLB were found to decrease significantly in subjects mutated for the TP53 and BRAF genes, while they increased in subjects mutated for KRAS, all compared to wild-type CRC patients. The role of the tumor suppressor p53, which is the product of the TP53 gene, has been widely demonstrated 30 . The protein is involved in cell cycle arrest, senescence, or apoptosis under cellular stress, as a consequence of DNA damage, hypoxia, and nutrient depletion.…”