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

Br J Cancer. 2019 Apr;120(8):797-805. doi: 10.1038/s41416-019-0429-2. Epub 2019 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Chemotherapy, Adjuvant / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin / administration & dosage
  • Progression-Free Survival
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult

Substances

  • Neoplasm Proteins
  • Organoplatinum Compounds
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Oxaliplatin
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol