Molecular alterations in metaplastic breast carcinoma

Cooper, Caroline; Karim, Rooshdiya Z.; Selinger, Christina; Carmalt, Hugh; Lee, C. Soon; O’Toole, Sandra A.

doi:10.1136/jclinpath-2012-201086

Cited by 30 publications

(29 citation statements)

References 86 publications

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“…Reduction in level of miR-200f, which is an important modulator of EMT, was found which further supports the association between MBC and EMT [15,16]. In the support of the hypothesis of the origin from stem cell are high CD44/CD24 and CD29/CD24 ratios in MBC, consistent with a high level of stem cell-like cells in these tumors [17].…”

Section: Discussionsupporting

confidence: 61%

Metaplastic carcinoma of the breast: an immunohistochemical study

et al. 2014

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BackgroundMetaplastic breast carcinoma is a rare entity of breast cancer expressing epithelial and/or mesenchymal tissue within the same tumor. The aim of this study is to evaluate the clinicopathological features of metaplastic breast carcinoma and to confirm the triple negative, basal-like and/or luminal phenotype of this type of tumor by using immunohistochemical staining.MethodsSeven cases of MBC were evaluated for clinico-pathological features including follow up data. Cases were studied immunohistochemically by CK-Pan, Vimentin, ER, PR, HER2, basal markers (CK5/6, p63, EGFR, SMA and S-100), luminal cytokeratins (CK8, CK18 and CK19), markers for syncytial cells (β-HCG and PLAP), as well as prognostic markers (p53, ki-67 and calretinin).ResultsThe mean age of the patients was 36 years. Three cases showed choriocarcinomatous features. All of our cases were negative for ER, PR and HER2. Six out of the 7 cases showed basal-like differentiation by demonstrating positivity with at least one of the basal/myoepithelial markers. Also 6 out of the 7 cases expressed luminal type cytokeratins (CK8, CK18 and/or CK19). P53 was positive in 3 cases, ki-67 was strongly expressed in only one case, while calretinin was expressed in 6 cases.ConclusionMetaplastic breast carcinoma presents in our population at a younger age group than other international studies. All cases are categorized immunohistochemically under the triple negative group of breast cancer and 86% of them exhibited basal-like and luminal phenotype. Majority of cases developed local recurrence and distant metastasis in a relatively short period of time.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1101289295115804

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Section: Discussionsupporting

confidence: 61%

Metaplastic carcinoma of the breast: an immunohistochemical study

et al. 2014

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“…[20][21][22] Metaplastic carcinomas of the breast have further been associated with the so-called claudin-low subtype of the basaloid phenotype in the molecular-portraits system. 23 In addition, mRNA profiling has linked the various histologic appearances of MPBC to various expression of a diverse group of genes.…”

Section: Resultsmentioning

confidence: 99%

Genomic Profiling of Advanced-Stage, Metaplastic Breast Carcinoma by Next-Generation Sequencing Reveals Frequent, Targetable Genomic Abnormalities and Potential New Treatment Options

Ross

Badve

Wang

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Metastatic metaplastic breast carcinoma (MPBC) is an uncommon, but aggressive, tumor resistant to conventional chemotherapy.Objective.-To learn whether next-generation sequencing could identify potential targets of therapy for patients with relapsed and metastatic MPBC.Design.-Hybridization capture of 3769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to a minimum of 50 ng of DNA extracted from 20 MPBC formalin-fixed, paraffinembedded specimens and sequenced to high uniform coverage.Results.-The 20 patients with MPBC had a median age of 62 years (range, 42-86 years). There were 9 squamous (45%), 9 chondroid (45%), and 2 spindle cell (10%) MPBCs, all of which were high grade. Ninety-three genomic alterations were identified, (range, 1-11) with 19 of the 20 cases (95%) harboring an alteration that could potentially lead to a targeted treatment option. The mostcommon alterations were in TP53 (n ¼ 69; 75%), PIK3CA (n ¼ 37; 40%), MYC (n ¼ 28; 30%), MLL2 (n ¼ 28; 30%), PTEN (n ¼ 23; 25%), CDKN2A/B (n ¼ 19; 20%), CCND3 (n ¼ 14; 15%), CCNE1 (n ¼ 9; 10%), EGFR (n ¼ 9; 10%), and KDM6A (n ¼ 9; 10%); AKT3, CCND1, CCND2, CDK4, FBXW7, FGFR1, HRAS, NF1, PIK3R1, and SRC were each altered in a single case. All 16 MPBCs (100%) that were negative for ERBB2 (HER2) overexpression by immunohistochemistry and/or ERBB2 (HER2) amplification by fluorescence in situ hybridization were also uniformly (100%) negative for ERBB2 amplification by next-generation sequencing-based copy-number assessment.Conclusions.-Our results indicate that genomic profiling using next-generation sequencing can identify clinically meaningful alterations that have the potential to guide targeted treatment decisions in most patients with metastatic MPBC.

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“…12,32 Metaplastic carcinomas also show enrichment in epithelial-mesenchymal transition and stem-cell like markers, with down-regulation of genes usually found in epithelial cells and up-regulation in genes found in mesenchymal cells such as fibroblasts. 33,34 Down-regulation of E-cadherin and activation of the Wnt pathway is a feature of this group. 34 Mutations in PI3K pathway genes is present in about half of cases.…”

Section: Molecular Findingsmentioning

confidence: 99%

“…33,34 Down-regulation of E-cadherin and activation of the Wnt pathway is a feature of this group. 34 Mutations in PI3K pathway genes is present in about half of cases. 32 EGFR amplification has been reported in a subset of metaplastic carcinomas.…”

Section: Molecular Findingsmentioning

confidence: 99%