Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer

BMC Cancer. 2019 May 9;19(1):429. doi: 10.1186/s12885-019-5631-3.

Abstract

Background: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data.

Methods: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data.

Results: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008).

Conclusions: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.

Keywords: Colorectal cancer; Minichromosome maintenance protein 6; Prognostic marker; Proliferative proteins; Topoisomerase II α.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Colon / pathology
  • Colon / surgery
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • DNA Topoisomerases, Type II / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 6 / metabolism*
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Prognosis
  • Rectum / pathology
  • Rectum / surgery
  • Retrospective Studies
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Poly-ADP-Ribose Binding Proteins
  • MCM6 protein, human
  • Minichromosome Maintenance Complex Component 6
  • DNA Topoisomerases, Type II
  • TOP2A protein, human