Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast

J Clin Pathol. 2004 Nov;57(11):1179-84. doi: 10.1136/jcp.2004.017434.

Abstract

Aims: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation.

Methods: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined.

Results: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p=0.0005).

Conclusions: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases
  • Ataxia Telangiectasia Mutated Proteins
  • Breast / pathology
  • Breast Diseases / genetics
  • Breast Diseases / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA Repair Enzymes / analysis
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods
  • MRE11 Homologue Protein
  • Muscle Cells / metabolism
  • Muscle Cells / pathology
  • Myoepithelioma / genetics*
  • Myoepithelioma / metabolism
  • Myoepithelioma / pathology
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Protein Serine-Threonine Kinases / analysis*
  • Protein Serine-Threonine Kinases / genetics
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MRE11 protein, human
  • NBN protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • RAD50 protein, human
  • DNA Repair Enzymes