title: Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum.
abstract: Secretory breast carcinomas (<0.15% of breast tumors) are associated with a characteristic morphology and a favorable prognosis. Remarkably, this entity is the only epithelial tumor of the breast with a balanced translocation, t(12;15), that creates an ETV6-NTRK3 gene fusion encoding chimeric tyrosine kinase also encountered in cellular mesoblastic nephroma and infantile fibrosarcoma. The aim of this study was to determine the phenotypic class (ie luminal A/B, ERBB2, basal-like) of secretory breast carcinoma. A series of six secretory breast carcinomas were identified in our files. The ETV6 rearrangement was confirmed in all cases by fluorescence in situ hybridization. Immunophenotype was assessed with anti-ER, PR, ERBB2, KIT, EGFR, E-cadherin, vimentin, PS100, smooth muscle actin, basal (CK5/6 and 14), luminal cytokeratins (CK8/18) and p63 antibodies. In situ and invasive components shared the same immunoprofile and were ER, PR, ERBB2 negative with expression of basal cytokeratins. ETV6 gene alterations were present in both in situ and invasive components, highlighting their genetic similarities. The immunoprofile data (triple-negative with expression of basal markers) showed that secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the phenotypic basal-like spectrum of breast carcinomas. These results support the hypothesis that secretory breast carcinomas have immunohistochemical and genetic features that distinguish them from other basal-like tumors of the breast.
authors.affiliation: Service de Pathologie, Section Médicale, Institut Curie, Paris Cedex, France.
authors.forename: Marick
authors.initials: M
authors.lastname: Laé
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Olfa
authors.initials: O
authors.lastname: Chouchane
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D014178:Translocation, Genetic; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein