title: Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast.
abstract: OBJECTIVE
  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.
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France.
authors.forename: S
authors.initials: S
authors.lastname: Angèle
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: J S
authors.initials: JS
authors.lastname: Reis Filho
authors.forename: L G
authors.initials: LG
authors.lastname: Fulford
authors.forename: I
authors.initials: I
authors.lastname: Treilleux
authors.forename: S R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: J
authors.initials: J
authors.lastname: Hall
mesh_terms: D017766:Acid Anhydride Hydrolases; D064007:Ataxia Telangiectasia Mutated Proteins; D001940:Breast / Q000473:pathology; D001941:Breast Diseases / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D000076228:MRE11 Homologue Protein; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009208:Myoepithelioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes