Expression of the mismatch repair protein hMSH2 in carcinoma in situ and invasive cancer of the breast

Anticancer Res. 2000 Jan-Feb;20(1A):119-24.

Abstract

Background: Dysregulations in the mechanism of DNA-repair are contributed to tumorgenesis and tumorprogression in human cancer. The mismatch repair gene hMSH2 encodes a protein, which recognizes and binds to mismatch-sequences of the DNA.

Methods: Using immunohistochemical techniques hMSH2 expression was analyzed in invasive cancer (n = 85) and in situ carcinoma (n = 34) of the breast.

Results: The percentage of hMSH2 positive cases was significantly (p = 0.0001) decreased in invasive cancer as compared to in situ carcinomas. There was an association of hMSH2 expression with parameters of unfavorable prognosis, such as lymph node involvement (p = 0.03), higher degree of malignancy (p = 0.05) and higher proliferative activity (p = 0.05).

Conclusions: During development from in situ to invasive cancer of the breast, hMSH2 expression seems to be downregulated. However, in invasive cancer, hMSH2 expression seems to be associated with tumor progression. This could be explained by the fact that enhanced proliferation of tumor cells results in increased mistakes within DNA replication procedures.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Antigens, Nuclear
  • Base Pair Mismatch*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / metabolism
  • DNA Repair*
  • DNA-Binding Proteins*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MutS Homolog 2 Protein
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • MSH2 protein, human
  • MutS Homolog 2 Protein