Low ATM protein expression in malignant tumor as well as cancer-associated stroma are independent prognostic factors in a retrospective study of early stage hormone negative breast cancer

IntroductionThe serine/threonine protein kinase ataxia telangiectasia mutated (ATM) is critical in maintaining genomic integrity. Upon DNA double-strand breaks, ATM phosphorylates key downstream proteins including p53 and BRCA1/2, thereby orchestrating complex signaling pathways involved in cell cycle arrest, DNA repair, senescence and apoptosis. Although sporadic mutation of ATM occurs rarely in breast cancer, the status of its protein expression and its clinical significance in breast cancer remain not well established. Our study was designed to investigate the influence of ATM protein in both tumor and cancer-associated stroma on clinical outcome in hormone positive (HPBC) and hormone negative (HNBC) early stage breast cancer (EBC). Methods: Tissue microarrays (TMA), containing formalin-fixed, paraffin embedded resected tumors from two cohorts of patients (HPBC cohort: n = 130; HNBC cohort: n = 168) diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, were analyzed for ATM protein expression using fluorescence immunohistochemistry (IHC) and automated quantitative analysis (AQUA). ATM expression levels were measured within the tumor as a whole (tATM) as indicated by pan-cytokeratin expression, tumor nuclear compartment (nATM) as indicated by both DAPI and pan-cytokeratin positive, and cancer associated stroma (csATM) as indicated by vimentin-positive and pan-cytokeratin-negative. ATM expression levels within these compartments were correlated with clinical out...
Source: Breast Cancer Research - Category: Cancer & Oncology Authors: Source Type: research