Ítem
Solo Metadatos
Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast
Título de la revista
Autores
Vranic, Semir
Marchiò, Caterina
Castellano, Isabella
Botta, Cristina
Scalzo, Maria Stella
Bender, Ryan P.
Payan-Gomez, Cesar
di Cantogno, Ludovica Verdun
Gugliotta, Patrizia
Tondat, Fabrizio
Fecha
2015
Directores
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Editor
W.B. Saunders
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Resumen
Abstract
Summary Despite the marked improvement in the understanding of molecular mechanisms and classification of apocrine carcinoma, little is known about its specific molecular genetic alterations and potentially targetable biomarkers. In this study, we explored immunohistochemical and molecular genetic characteristics of 37 invasive apocrine carcinomas using immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS) assays. IHC revealed frequent E-cadherin expression (89%), moderate (16%) proliferation activity [Ki-67, phosphohistone H3], infrequent (~10%) expression of basal cell markers [CK5/6, CK14, p63, caveolin-1], loss of PTEN (83%), and overexpression of HER2 (32%), EGFR (41%), cyclin D1 (50%), and MUC-1 (88%). MLPA assay revealed gene copy gains of MYC, CCND1, ZNF703, CDH1, and TRAF4 in 50% or greater of the apocrine carcinomas, whereas gene copy losses frequently affected BRCA2 (75%), ADAM9 (54%), and BRCA1 (46%). HER2 gain, detected by MLPA in 38% of the cases, was in excellent concordance with HER2 results obtained by IHC/FISH (? = 0.915, P less than .001). TOP2A gain was observed in one case, while five cases (21%) exhibited TOP2A loss. Unsupervised hierarchical cluster analysis revealed two distinct clusters: HER2-positive and HER2-negative (P =.03 and.04, respectively). NGS assay revealed mutations of the TP53 (2 of 7, 29%), BRAF/KRAS (2 of 7, 29%), and PI3KCA/PTEN genes (7 of 7, 100%). We conclude that morphologically defined apocrine carcinomas exhibit complex molecular genetic alterations that are consistent with the 'luminal-complex' phenotype. Some of the identified molecular targets are promising biomarkers; however, functional studies are needed to prove these observations. © 2015 Elsevier Inc.
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Keywords
B Raf kinase , Neoplastic , BRCA1 protein , Biological , Fluorescence , BRCA2 protein , Caveolin 1 , Cell cycle protein 6 , Cyclin D1 , Cytokeratin 14 , Cytokeratin 5 , Cytokeratin 6 , DNA topoisomerase (ATP hydrolysing) A , Epidermal growth factor receptor , Epidermal growth factor receptor 2 , Estrogen receptor , Fizzy related protein , K ras protein , Ki 67 antigen , Mucin 1 , Myc protein , Phosphatidylinositol 3 kinase , Phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase , Progesterone receptor , Protein p53 , Protein p63 , Tumor necrosis factor receptor associated factor 4 , Uvomorulin , Tumor marker , Apocrine carcinoma , Basal cell , Breast carcinoma , Cell proliferation , Chromosome 17q , Clinical article , Cluster analysis , Conference Paper , Fluorescence in situ hybridization , Gene dosage , Gene mutation , Gene overexpression , Genetic trait , Histology , Human , Human tissue , Immunohistochemistry , Immunophenotyping , Mitosis rate , Multiplex ligation dependent probe amplification , Next generation sequencing , Protein expression , Apocrine gland , Breast Neoplasms , Carcinoma , Chemistry , Comparative study , Female , Gene expression regulation , Genetic predisposition , Genetics , High throughput sequencing , Molecular diagnosis , Multiplex polymerase chain reaction , Pathology , Phenotype , Predictive value , Sweat Gland Neoplasms , Apocrine Glands , Breast Neoplasms , Carcinoma , Cluster Analysis , Female , Gene Expression Regulation , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , In Situ Hybridization , Molecular Diagnostic Techniques , Multiplex Polymerase Chain Reaction , Phenotype , Predictive Value of Tests , Sweat Gland Neoplasms , Tumor Markers , Androgen receptor , Breast carcinoma-apocrine carcinoma , Fluorescent in situ hybridization , Immunohistochemistry , Multiplex ligation-dependent probe amplification , Next-generation sequencing
