DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study

J Cancer Res Clin Oncol. 2002 Dec;128(12):650-8. doi: 10.1007/s00432-002-0394-6. Epub 2002 Nov 15.

Abstract

Purpose: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis.

Methods: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis.

Results: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death.

Conclusions: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / pathology
  • Adenocarcinoma, Mucinous / surgery
  • Biomarkers, Tumor / analysis
  • Cell Division
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • DNA, Neoplasm / genetics*
  • Disease-Free Survival
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Monomeric GTP-Binding Proteins / genetics*
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Staging
  • Nucleoside-Diphosphate Kinase*
  • Ploidies*
  • Predictive Value of Tests
  • S Phase
  • Survival Analysis
  • Time Factors
  • Transcription Factors / genetics*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • NM23 Nucleoside Diphosphate Kinases
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins