TY - JOUR
T1 - Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast
AU - Vranic, Semir
AU - Marchiò, Caterina
AU - Castellano, Isabella
AU - Botta, Cristina
AU - Scalzo, Maria Stella
AU - Bender, Ryan P.
AU - Payan-Gomez, Cesar
AU - Di Cantogno, Ludovica Verdun
AU - Gugliotta, Patrizia
AU - Tondat, Fabrizio
AU - Di Celle, Paola Francia
AU - Mariani, Sara
AU - Gatalica, Zoran
AU - Sapino, Anna
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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 (κ = 0.915, P
AB - 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 (κ = 0.915, P
KW - Androgen receptor
KW - Breast carcinoma-apocrine carcinoma
KW - Fluorescent in situ hybridization
KW - Immunohistochemistry
KW - Multiplex ligation-dependent probe amplification
KW - Next-generation sequencing
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U2 - 10.1016/j.humpath.2015.05.017
DO - 10.1016/j.humpath.2015.05.017
M3 - Article
C2 - 26208846
AN - SCOPUS:84940462439
VL - 46
SP - 1350
EP - 1359
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 9
ER -