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00925njm 22002777a 4500 dc Palacios, José author Honrado, Emiliano author Osorio, Ana author Cazorla, Alicia author Sarrió, David author Barroso, Alicia author Rodriguez Perales, Sandra author Cigudosa, Juan C author Diez, Orland author Alonso, Carmen author Lerma, Enrique author Dopazo, Joaquín author Rivas, Carmen author Benítez, Javier author 2005-03 Familial breast cancers that are associated with BRCA1 or BRCA2 germline mutations differ in both their morphological and immunohistochemical characteristics. To further characterize the molecular difference between genotypes, the authors evaluated the expression of 37 immunohistochemical markers in a tissue microarray (TMA) containing cores from 20 BRCA1, 14 BRCA2, and 59 sporadic age-matched breast carcinomas. Markers analyzed included, amog others, common markers in breast cancer, such as hormone receptors, p53 and HER2, along with 15 molecules involved in cell cycle regulation, such as cyclins, cyclin dependent kinases (CDK) and CDK inhibitors (CDKI), apoptosis markers, such as BCL2 and active caspase 3, and two basal/myoepithelial markers (CK 5/6 and P-cadherin). In addition, we analyzed the amplification of CCND1, CCNE, HER2 and MYC by FISH. Unsupervised cluster data analysis of both hereditary and sporadic cases using the complete set of immunohistochemical markers demonstrated that most BRCA1-associated carcinomas grouped in a branch of ER-, HER2-negative tumors that expressed basal cell markers and/or p53 and had higher expression of activated caspase 3. The cell cycle proteins associated with these tumors were E2F6, cyclins A, B1 and E, SKP2 and Topo IIalpha. In contrast, most BRCA2-associated carcinomas grouped in a branch composed by ER/PR/BCL2-positive tumors with a higher expression of the cell cycle proteins cyclin D1, cyclin D3, p27, p16, p21, CDK4, CDK2 and CDK1. In conclusion, our study in hereditary breast cancer tumors analyzing 37 immunohistochemical markers, define the molecular differences between BRCA1 and BRCA2 tumors with respect to hormonal receptors, cell cycle, apoptosis and basal cell markers. Full text links Springer full text link Actions Share Page navigation Title & authors Abstract Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Breast Cancer Res Treat . 2005 Mar;90(1):5-14. Breast Cancer Res Treat 15770521 https://hdl.handle.net/20.500.12105/26233 tissue microarray immunohistochemistry cell cycle BRCA2 BRCA1 BASAL PHENOTYPE Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers.