p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy

Abstract

BACKGROUND: We attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC). METHODS: We analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression. RESULTS: The distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60-4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28-6.57, P = 0.011). CONCLUSIONS: p53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

“…Although the finding did not achieve statistical significance due to the small cohort size, there are several pieces of additional evidences in the literature for consideration. For example, a recent publication, Oh et al 24 has found a low-expression of TP53 protein was associated with poor cancer-specific survival in Stage III and high-rick Stage II CRC patients (N = 621) who were treated with oxaliplatin-based adjuvant chemotherapy. Additionally, using the TCGA cohort, we found TP53 copy number loss were significantly associated with lower mRNA expression level (P < 1e-15, one tailed T-test on Z-normalized mRNA expression levels, see Supplementary Fig.…”

Diabetes associated with abnormal p53 immunohistochemical patterns in colorectal cancer

“…Although not all abnormal p53 IHC patterns is caused by TP53 mutation, the fact that all the 3 abnormal p53 IHC patterns were signi cantly associated with T2DM in the present study was highly suggestive for a link between T2DM and TP53 mutation. In a recent study [26], the rate of TP53 nonsynonymous SNVs (mutation) were found in 80.2% of p53-strong expression group (> 50% of tumor cells were positive), while rates of stop-gain mutation and indels were found in 38.2% and 14.7% of p53-no group (complete absence) of CRC. In another study using 20% as cut-off value for p53 positive [27], TP53 mutation was found in 79.6% (39/49) of p53 positive CRC and 97.4% (38/39) of the mutation was missense mutation.…”

Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

“…Although the finding did not achieve statistical significance due to the small cohort size, there are several pieces of additional evidences in the literature for consideration. For example, a recent publication, Oh et al 24 has found a low-expression of TP53 protein was associated with poor cancer-specific survival in Stage III and high-rick Stage II CRC patients (N=621) who were treated with oxaliplatin-based adjuvant chemotherapy. Additionally, using the TCGA cohort, we found TP53 copy number loss were significantly associated with lower mRNA expression level (P<1e-15, one tailed T-test on Z-normalized mRNA expression levels, see Figure S3).…”