Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum

Abstract

Secretory breast carcinomas (o0.15% 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.

Secretory breast carcinoma: a clinicopathological and immunophenotypic study of 15 cases with a review of the literature

“…prognosis. 7 This view is confirmed by our present study. However, the clinical significance of this finding is not clear at this time.…”

“…7 In this retrospective study, 15 cases of secretory breast carcinoma were retrieved from a series of 10 000 newly diagnosed breast cancers between 2006 and 2010, with an incidence of only 0.15%. The reported male-female ratio is approximately 1:6, 9 which is similar to the distribution in our data set.…”

“…3,4 Immunochemically, the tumor usually has shown strong reactivity for S-100 and is negative for estrogen receptor (ER), progesterone receptor (PR) and HER2. [4][5][6][7] In 2002, Tognon et al 8 were the first to report that secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion in 12 out of 13 of their cases. Recently, Laé et al 7 demonstrated that secretory breast carcinoma with the ETV6-NTRK3 fusion gene belongs to the phenotypic spectrum of basal-like breast carcinomas, and immunohistochemical, as well as genetic features of secretory breast carcinomas, distinguished them from other basal-like breast cancers.…”

Secretory Carcinoma of Breast in a Patient Treated for Differentiated Thyroid Carcinoma—A Diagnostic Dilemma

“…These neoplasms can have late local recurrences but is generally associated with prolonged survival, even with axillary lymphnode involvement [3,4]. Immunochemically, the tumor usually shows strong reactivity for S-100 but is negative for estrogen receptor (ER), progesterone receptor (PR) and HER2 neu protein [5][6][7]. In 2002, Tognon et al [8] reported that secretory breast carcinoma expressed the ETV6-NTRK3 gene fusion in 12 out of 13 of their cases, which is now considered to be a differentiating factor from other basal-like breast cancers.…”

Secretory carcinoma — impact of translocation and gene fusions on salivary gland tumor

“…It occurs more often in younger women than in elderly women (3). Molecularly, mammary SC is the only epithelial tumor with the t(12;15)(p13;q25) translocation in breast, leading to a fusion of the ETV6 gene from chromosome 12 and the NTRK3 gene from chromosome 15 (4,5). The ETV6-NTRK3 fusion gene encodes a chimeric tyrosine kinase, and this fusion results in a constitutively active chimeric tyrosine kinase mitogenic pathway and the phosphatidyl inositol-3-kinase (PI3K)-AKT pathway (6,7).…”