Abstract

BackgroundWe 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).MethodsWe 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.ResultsThe 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).Conclusionsp53-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.

Highlights

  • 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)

  • Clinicopathologic characteristics of CRCs according to p53 expression status or TP53 genotype The clinicopathologic characteristics of CRCs according to p53 expression status and TP53 genotype are summarised in Tables 1 and 2. p53-no, p53-mild, p53-moderate and p53-strong expression was found in 123 (19.8%), 68 (11.0%), 110 (17.7%) and 320 (51.5%) patients, respectively (Figs. 1 and 2a)

  • In terms of the molecular aspect, the p53-mild and p53-moderate expression groups were associated with Microsatellite instability (MSI)-H (P < 0.001), high frequency of CIMP-P1 or CIMP-P2 (P < 0.001), MLH1 methylation (P < 0.001), aberrant CK7 expression (P = 0.013) and decreased CDX2 expression (P < 0.001)

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Summary

Introduction

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). CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression. The presence of wild-type TP53 in cell lines was associated with in vitro growth inhibition in response to many chemotherapeutic agents, including DNA/RNA antimetabolites, alkylating agents and topoisomerase I and II inhibitors.[9,10,11] TP53 is a tumour-suppressor gene, TP53 mutations can be either ‘gain of function' (GOF) mutations or ‘loss of function' (LOF) mutations. Many studies have attempted to correlate p53 expression status with prognosis or therapeutic response in CRC but have yielded inconsistent results regarding those relationships.[12,13,14,15,16,17,18,19] the cutoff values that define p53 overexpression according to immunohistochemistry are Received: 28 September 2018 Revised: 26 February 2019 Accepted: 1 March 2019 Published online: 21 March 2019

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