Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil-leucovorin combination

Ann Oncol. 2000 Aug;11(8):1053-6. doi: 10.1023/a:1008362511552.

Abstract

Background: We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination.

Patients and methods: The study population consisted of 41 patients with unresectable metastatic colon cancer, homogeneously, treated with bolus 5-FU and LV.

Results: Twenty-seven patients (66%) showed high levels of TS expression. The difference in the proportion of objective responses between patients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was statistically significant (P = 0.0001, chi-square test). p53 nuclear over-expression was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients with low TS expression.

Conclusions: p53 status measured by immunohistochemistry does not seem to be useful to identify unresponsive patients with low TS expression.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / immunology
  • Female
  • Fluorouracil / administration & dosage
  • Genes, p53 / genetics*
  • Humans
  • Immunohistochemistry
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Thymidylate Synthase / analysis*
  • Thymidylate Synthase / metabolism
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Protein p53
  • Thymidylate Synthase
  • Leucovorin
  • Fluorouracil