Immunohistochemistry of proteins for DNA mismatch repair in correlation to prognostic factors of mammarian cancer

Oncol Rep. 2007 May;17(5):1223-7.

Abstract

Mutations in genes of the DNA mismatch repair system (MMR) are strongly linked to the development of hereditary non-polyposis colorectal cancer and play a significant role in sporadic cancer too. Besides the repair of chromosomal mismatches produced during replication, the MMR is the linkage of DNA mismatches to cell cycle control. Proteins of the MMR are necessary for the induction of apoptosis in response to non-tolerable amounts of DNA damage. We correlated the immunoreactivity of the MMR proteins hMSH2, hMLH1 and PMS2 to the immunoreaction of p53, the proliferation marker Ki67 and clinical prognosis factors such as tumor grading and staging, steroid receptor expression and hemangiosis carcinomatosa or lymphangiosis carcinomatosa in 200 samples from patients with diagnosed breast cancer. No correlation could be detected among the expression of the three MMR-proteins hMSH2, hMLH1 and PMS2. The expression of hMSH2 correlated positively with the expression of p53, with the appearance of distant metastases, low differentiation and the appearance of hemangiosis carcinomatosa and lymphangiosis carcinomatosa, while it negatively correlated with the expression of the estrogen receptor. No correlation was detected between hMLH1 or PMS2 and any of the investigated factors. The expression of hMSH2 seems to be related with predictors of an unfavorable course of disease in breast cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics
  • Adenosine Triphosphatases / biosynthesis
  • Adenosine Triphosphatases / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / biosynthesis
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Ki-67 Antigen / genetics
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / biosynthesis
  • MutS Homolog 2 Protein / genetics
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Prognosis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • MLH1 protein, human
  • Nuclear Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes