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

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.

Altered expression of anti-apoptotic proteins in non-involved tissue from cancer-containing breasts

“…Hsp 27 has also been shown to have an anti-apoptotic role [34]. It can increase cell survival in response to apoptotic stimuli, activate protein kinase B, an apoptotic inhibitor [41,42]. In the present study no significant differences were found for BRCA1, ATM and BARD1 immunoreactivity between normal breast from cancer-containing breasts and non-cancerous breasts.…”

Adenomyoepithelioma of the breast: a review stressing its propensity for malignant transformation

“…Allelic imbalance and microsatellite instability have also been described in AME 65. Expression of ATM, p53 and the MRE11-Rad50-NBS1 complex has been detected in myoepithelial cells from both benign and malignant proliferations of the breast and is not specific for AME 66. There is one case report of AME arising in association with neurofibromatosis but there is no other association with familial tumour syndromes 67.…”

Myoepithelial cells: good fences make good neighbors

“…Recently, Angele and coworkers [61] found that human luminal and myoepithelial cells differ in their DNA repair capacity, and this may contribute to the lower rate of transformation in myoepithelial cells. Additionally, when they do undergo transformation, they usually form benign or low-grade neoplasms.…”