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Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast

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dc.creatorVranic, Semirspa
dc.creatorMarchiò, Caterinaspa
dc.creatorCastellano, Isabellaspa
dc.creatorBotta, Cristinaspa
dc.creatorScalzo, Maria Stellaspa
dc.creatorBender, Ryan P.spa
dc.creatorPayan-Gomez, Cesarspa
dc.creatordi Cantogno, Ludovica Verdunspa
dc.creatorGugliotta, Patriziaspa
dc.creatorTondat, Fabriziospa
dc.creatordi Celle, Paola Franciaspa
dc.creatorMariani, Saraspa
dc.creatorGatalica, Zoranspa
dc.creatorSapino, Annaspa
dc.date.accessioned2020-05-26T00:10:28Z
dc.date.available2020-05-26T00:10:28Z
dc.date.created2015spa
dc.description.abstractSummary 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.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1016/j.humpath.2015.05.017
dc.identifier.issn468177
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24230
dc.language.isoengspa
dc.publisherW.B. Saundersspa
dc.relation.citationEndPage1359
dc.relation.citationIssueNo. 9
dc.relation.citationStartPage1350
dc.relation.citationTitleHuman Pathology
dc.relation.citationVolumeVol. 46
dc.relation.ispartofHuman Pathology, ISSN:468177, Vol.46, No.9 (2015); pp. 1350-1359spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84940462439&doi=10.1016%2fj.humpath.2015.05.017&partnerID=40&md5=45106789d401c1d69029b8f69f5ffb68spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordB Raf kinasespa
dc.subject.keywordNeoplasticeng
dc.subject.keywordBRCA1 proteinspa
dc.subject.keywordBiologicaleng
dc.subject.keywordFluorescenceeng
dc.subject.keywordBRCA2 proteinspa
dc.subject.keywordCaveolin 1spa
dc.subject.keywordCell cycle protein 6spa
dc.subject.keywordCyclin D1spa
dc.subject.keywordCytokeratin 14spa
dc.subject.keywordCytokeratin 5spa
dc.subject.keywordCytokeratin 6spa
dc.subject.keywordDNA topoisomerase (ATP hydrolysing) Aspa
dc.subject.keywordEpidermal growth factor receptorspa
dc.subject.keywordEpidermal growth factor receptor 2spa
dc.subject.keywordEstrogen receptorspa
dc.subject.keywordFizzy related proteinspa
dc.subject.keywordK ras proteinspa
dc.subject.keywordKi 67 antigenspa
dc.subject.keywordMucin 1spa
dc.subject.keywordMyc proteinspa
dc.subject.keywordPhosphatidylinositol 3 kinasespa
dc.subject.keywordPhosphatidylinositol 3,4,5 trisphosphate 3 phosphatasespa
dc.subject.keywordProgesterone receptorspa
dc.subject.keywordProtein p53spa
dc.subject.keywordProtein p63spa
dc.subject.keywordTumor necrosis factor receptor associated factor 4spa
dc.subject.keywordUvomorulinspa
dc.subject.keywordTumor markerspa
dc.subject.keywordApocrine carcinomaspa
dc.subject.keywordBasal cellspa
dc.subject.keywordBreast carcinomaspa
dc.subject.keywordCell proliferationspa
dc.subject.keywordChromosome 17qspa
dc.subject.keywordClinical articlespa
dc.subject.keywordCluster analysisspa
dc.subject.keywordConference Paperspa
dc.subject.keywordFluorescence in situ hybridizationspa
dc.subject.keywordGene dosagespa
dc.subject.keywordGene mutationspa
dc.subject.keywordGene overexpressionspa
dc.subject.keywordGenetic traitspa
dc.subject.keywordHistologyspa
dc.subject.keywordHumanspa
dc.subject.keywordHuman tissuespa
dc.subject.keywordImmunohistochemistryspa
dc.subject.keywordImmunophenotypingspa
dc.subject.keywordMitosis ratespa
dc.subject.keywordMultiplex ligation dependent probe amplificationspa
dc.subject.keywordNext generation sequencingspa
dc.subject.keywordProtein expressionspa
dc.subject.keywordApocrine glandspa
dc.subject.keywordBreast Neoplasmsspa
dc.subject.keywordCarcinomaspa
dc.subject.keywordChemistryspa
dc.subject.keywordComparative studyspa
dc.subject.keywordFemalespa
dc.subject.keywordGene expression regulationspa
dc.subject.keywordGenetic predispositionspa
dc.subject.keywordGeneticsspa
dc.subject.keywordHigh throughput sequencingspa
dc.subject.keywordMolecular diagnosisspa
dc.subject.keywordMultiplex polymerase chain reactionspa
dc.subject.keywordPathologyspa
dc.subject.keywordPhenotypespa
dc.subject.keywordPredictive valuespa
dc.subject.keywordSweat Gland Neoplasmsspa
dc.subject.keywordApocrine Glandsspa
dc.subject.keywordBreast Neoplasmsspa
dc.subject.keywordCarcinomaspa
dc.subject.keywordCluster Analysisspa
dc.subject.keywordFemalespa
dc.subject.keywordGene Expression Regulationeng
dc.subject.keywordGenetic Predisposition to Diseasespa
dc.subject.keywordHigh-Throughput Nucleotide Sequencingspa
dc.subject.keywordHumansspa
dc.subject.keywordImmunohistochemistryspa
dc.subject.keywordIn Situ Hybridizationeng
dc.subject.keywordMolecular Diagnostic Techniquesspa
dc.subject.keywordMultiplex Polymerase Chain Reactionspa
dc.subject.keywordPhenotypespa
dc.subject.keywordPredictive Value of Testsspa
dc.subject.keywordSweat Gland Neoplasmsspa
dc.subject.keywordTumor Markerseng
dc.subject.keywordAndrogen receptorspa
dc.subject.keywordBreast carcinoma-apocrine carcinomaspa
dc.subject.keywordFluorescent in situ hybridizationspa
dc.subject.keywordImmunohistochemistryspa
dc.subject.keywordMultiplex ligation-dependent probe amplificationspa
dc.subject.keywordNext-generation sequencingspa
dc.titleImmunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breastspa
dc.typeconferenceObjecteng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaDocumento de conferenciaspa
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