Relationship of mismatch repair proteins and survivin in colon polyps and carcinomas

Acta Histochem. 2014 Jul;116(6):1007-14. doi: 10.1016/j.acthis.2014.04.005. Epub 2014 May 20.

Abstract

Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the production of abnormally short or inactivated proteins. The antiapoptotic protein survivin functions in the inhibition of apoptosis, regulation of cell division and also enhances angiogenesis. Both MMRP and survivin are considered to be powerful prognostic parameters. This study was designed to determine the relationship between MMRP and survivin in colon lesions. The study included 113 cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and MMRP status were assessed by immunohistochemistry. In each section, expression, intensity of immunostaining and percentage of labeled cells were analyzed. In carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%), 112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical analysis confirmed a significant correlation between the expression of MMRP and survivin in the assessed parameters. All 51 polyp samples were positive for MLH1, MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin. Statistically significant differences were observed between the expression of MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the antiapoptotic function of survivin through p53 inactivation of its promoter in grade 1 and grade 2 colon carcinomas.

Keywords: Colon carcinomas; Colon polyps; Mismatch repair proteins; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenocarcinoma / enzymology*
  • Adenosine Triphosphatases / metabolism
  • Aged
  • Aged, 80 and over
  • Colonic Neoplasms / enzymology*
  • Colonic Polyps / enzymology*
  • DNA Mismatch Repair
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Male
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutL Proteins
  • MutS Homolog 2 Protein / metabolism
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Survivin

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC5 protein, human
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Inhibitor of Apoptosis Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • PMS1 protein, human
  • Survivin
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutL Proteins
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes