title: Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers.
abstract: 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.
authors.affiliation: Breast and Gynaecological Cancer Laboratory, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.forename: Emiliano
authors.initials: E
authors.lastname: Honrado
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Alicia
authors.initials: A
authors.lastname: Cazorla
authors.forename: David
authors.initials: D
authors.lastname: Sarrió
authors.forename: Alicia
authors.initials: A
authors.lastname: Barroso
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodríguez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Orland
authors.initials: O
authors.lastname: Diez
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Enrique
authors.initials: E
authors.lastname: Lerma
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: Carmen
authors.initials: C
authors.lastname: Rivas
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins; D016000:Cluster Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D010641:Phenotype; D013030:Spain; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins