ORIGINAL ARTICLE

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

S Angèle¹, C Jones², J S Reis Filho², L G Fulford², I Treilleux³, S R Lakhani^2,4, J Hall¹

¹ International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France
² The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK
³ Centre Régional Léon Bérard, 28 rue Laennec, 69008 Lyon, France
⁴ Molecular and Cellular Pathology, School of Medicine, University of Queensland, Mayne Medical School, Herston Road, Herston, Brisbane, QLD 4006, Australia

Correspondence to:
Correspondence to:
Dr J Hall
DNA Repair Team, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France; hall{at}iarc.fr

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.

Abbreviations: SMA, smooth muscle actin; ATM, ataxia telangiectasia mutated; CK, cytokeratin; ER, oestrogen receptor; MRN, complex of MRE11, Rad50 and NBS1 proteins; MRE11, meiotic recombination 11 homologue; NBS, Nijmegen breakage syndrome

Keywords: breast; myoepithelial cells; DNA repair; immunohistochemistry

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