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pubmed-article:21785684pubmed:abstractTextTo detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and "budding-uninhibited-by-benzimidazoles-1-homolog-beta" (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; N = 9) and high-grade molecular abnormality (HNB-HGMA; N = 9). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0-300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.lld:pubmed
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pubmed-article:21785684pubmed:issn2042-003Xlld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:McCarthySusan...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:YeatmanTimoth...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:HarrisEleanor...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:ChenDung-TsaD...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:NasirAejazAlld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:VenkataramuCh...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:KhakpourNazan...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:GruidlMikeMlld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:McBrideHeyoun...lld:pubmed
pubmed-article:21785684pubmed:authorpubmed-author:Henderson-Jac...lld:pubmed
pubmed-article:21785684pubmed:issnTypeElectroniclld:pubmed
pubmed-article:21785684pubmed:volume2011lld:pubmed
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pubmed-article:21785684pubmed:pagination489064lld:pubmed
pubmed-article:21785684pubmed:year2011lld:pubmed
pubmed-article:21785684pubmed:articleTitleNovel molecular markers of malignancy in histologically normal and benign breast.lld:pubmed
pubmed-article:21785684pubmed:affiliationDepartment of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.lld:pubmed
pubmed-article:21785684pubmed:publicationTypeJournal Articlelld:pubmed