Epithelial–mesenchymal transition in breast cancer correlates with high histological grade and triple‐negative phenotype

Jeong, Hoiseon; Ryu, Young Joon; An, Jungsuk; Lee, Youngseok; Kim, Aeree

doi:10.1111/j.1365-2559.2012.04195.x

Cited by 87 publications

(83 citation statements)

References 36 publications

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“…Moreover, β-catenin was significantly related to ER (+), PR (+) and lower histological grade. A battery of studies uncovering the similar results [11,50] implied the actual association between EMT and TNBC.…”

Section: Discussionmentioning

confidence: 65%

“…We concluded that vimentin was more frequent in TNBC compared to E-cadherin and β-catenin which were prevalent in Luminal set. In Hoiseon's [50] study, 25.4% of TN-type patients were vimentin-positive, and decreased Ecadherin expression was seen in 16.7% TNBC. However, the corresponding data was 4.1% and 11.8% in hormone receptorpositive cases, respectively.…”

Section: Discussionmentioning

confidence: 99%

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MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

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Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.59%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of β-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and β-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

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“…During tumor growth and progression, the local microenvironment and growth factors may induce epithelial tumor cells to dedifferentiate and acquire an epithelial mesenchymal transition like phenotype characterized by loss of cell to cell adhesion, down regulation of E-cadherin and a shift of intermediate filaments to vimentin [25]. Suppression of CK19 expression in carcinomas during tumor differentiation has been reported in both human tissues, such as breast cancers, and cultured malignant cell lines [26,27]. Down-regulation of CK19 expression and overexpression of vimentin were found in highly aggressive breast cancer cells with strong migratory and invasive abilities [28].…”

Section: Discussionmentioning

confidence: 99%

Acantholytic Squamous Cell Carcinoma in Upper Aerodigestive Tract: Histopathology, Immunohistochemical Profile and Epithelial Mesenchymal Transition Phenotype Change

Jiang

Fowler

2012

Head and Neck Pathol

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Acantholytic squamous cell carcinoma is a rare variant of squamous cell carcinoma in the mucosa of upper aerodigestive tract. Histomorphologically, acantholytic squamous cell carcinoma may lose the typical features of conventional squamous cell carcinoma and mimic other epithelial or mesenchymal malignancies due to advanced acantholysis and dyskeratosis. Because of its rarity, information of prognosis, pathologic features and immunohistochemical profiles is limited. We have studied clinicopathologic features and immunohistochemical profiles of four acantholytic squamous cell carcinoma cases arising from upper aerodigestive tract. Clinical results indicate an aggressive biologic behavior. Morphologically, all tumors revealed significant acantholysis with separation of tumor cells and intratumoral spaces. The tumor cells were highly pleomorphic and growth patterns were variable. In immunohistochemical studies, all tumor cells revealed positive reactions for AE1/AE3 and p63 supporting a squamous epithelial origin. In contrast to conventional aerodigestive squamous cell carcinoma, acantholytic squamous cell carcinoma showed significant reductions of cytokeratin19, E-cadherin and concomitant up-regulation of vimentin expression. Both morphologic features and immunohistochemical profiles indicate that acantholytic squamous cell carcinoma has acquired an epithelial mesenchymal transition phenotype. However, in contrast to other solid malignant tumors, the epithelial mesenchymal transition phenotype change in acantholytic squamous cell carcinoma is not limited to the invasive front of the peripheral tumor but, rather, diffusely involves entire neoplastic lesion. In addition, because cytokeratin 19 staining is attenuated, this would be an insensitive marker for following up and/or in detecting disseminated tumor cells in cases of acantholytic squamous cell carcinoma in upper aerodigestive tract.

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“…Four data sets showed that FZD10 expression is negatively correlated with BRMS1L (Supplementary Table 3). In addition, oncomine database showed that triple negative breast cancers that tend to present stronger mesenchymal phenotype 36 and Wnt pathway activation 37 have higher FZD10 expression than other breast cancer subtypes (Supplementary Table 3). Collectively, these data suggest that BRMS1L inhibits EMT and invasiveness of breast cancer cells via downregulation of FZD10.…”

Section: Reduced Brms1l Is Associated With Breast Cancer Metastasismentioning

confidence: 99%

BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

Gong

et al. 2014

Nat Commun

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BRMS1L (breast cancer metastasis suppressor 1 like, BRMS1-like) is a component of Sin3A-histone deacetylase (HDAC) co-repressor complex that suppresses target gene transcription. Here we show that reduced BRMS1L in breast cancer tissues is associated with metastasis and poor patient survival. Functionally, BRMS1L inhibits breast cancer cells migration and invasion by inhibiting epithelial-mesenchymal transition. These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signalling, through HDAC1 recruitment and histone H3K9 deacetylation at the promoter. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-b-catenin signalling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNA interference-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, whereas ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signalling in breast cancer cells and acts as a breast cancer metastasis suppressor.

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Epithelial–mesenchymal transition in breast cancer correlates with high histological grade and triple‐negative phenotype

Abstract: EMT features were particularly seen in TN-type breast cancer (P < 0.001). EMT was also significantly associated with high histological grade (P < 0.001).

Cited by 87 publications

References 36 publications

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Acantholytic Squamous Cell Carcinoma in Upper Aerodigestive Tract: Histopathology, Immunohistochemical Profile and Epithelial Mesenchymal Transition Phenotype Change

BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

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