Metaplastic breast carcinoma:series of cases and literature review

Introduction: Metaplastic breast carcinoma is a heterogeneous group of infrequent invasive carcinomas with aggressive behavior. It presents differentiation from the neoplastic ductal epithelium to squamous and/or sarcomatous mesenchymal component, through the epithelial-mesenchymal transition process, and may present morphology of epithelioid and fusiform cells, with possible cartilage, bone, lipomatous, fibromatous, smooth muscle or skeletal muscle differentiation, among others. Most of the cases present the triple-negative immunohistochemical profile. Objective: To report three cases of metaplastic carcinomas, with an emphasis on clinical and pathological aspects, in addition to conducting a literature review on this topic. Methods: The three cases were registered in the internal search system for reference services in breast pathology in São Paulo, between 2012 and 2019. For literature review, the keywords metaplastic carcinoma, breast, cancer, review, breast cancer subtype and pathological and clinical outcomes were used in PubMed. We found 154 articles, of which 42 were selected for full reading, based on the abstract and established inclusion criteria. After this initial selection, these articles were read and reviewed; nine articles that did not meet the inclusion criteria were excluded. Discussion: Three cases of metaplastic carcinoma with similar immunohistochemical characteristics have been reported. The first case is that of a 40-year-old patient with the diagnosis of metaplastic carcinoma producing a chondroid matrix with liposarcomatous and osteosarcomatous differentiation. The second case is that of a 50-year-old patient who presented with the final diagnosis for a fusocellular metaplastic carcinoma with lymph node metastasis. Finally, the third case described is that of a 59-year-old patient, who presented metaplastic carcinoma with chondroid differentiation. Conclusion: Metaplastic carcinoma is a rare and aggressive type of breast cancer, in which most of the patients have shorter survival and worse prognosis in relation to the other subtypes. More studies are needed in order to determine a gold standard treatment for this disease.

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miR-144 functions as a tumor suppressor in breast cancer through inhibiting ZEB1/2-mediated epithelial mesenchymal transition process

OncoTargets and Therapy ◽

10.2147/ott.s103650 ◽

2016 ◽

Vol Volume 9 ◽

pp. 6247-6255 ◽

Cited By ~ 27

Author(s):

Yuliang Pan ◽

Jun Zhang ◽

Huiqun Fu ◽

Liangfang Shen

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Mesenchymal Transition

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Evaluation of Androgen Receptor in Relation to Estrogen Receptor (AR/ER) and Progesterone Receptor (AR/PgR): A New Must in Breast Cancer?

Journal of Oncology ◽

10.1155/2019/1393505 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Giuseppe Bronte ◽

Andrea Rocca ◽

Sara Ravaioli ◽

Emanuela Scarpi ◽

Massimiliano Bonafè ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Survival Data ◽

Epithelial Mesenchymal Transition ◽

Case Series ◽

Transition Process ◽

Primary Tumors ◽

Mesenchymal Transition ◽

Early Primary ◽

Patient Prognosis

Steroid nuclear receptors are known to be involved in the regulation of epithelial-mesenchymal transition process with important roles in invasion and metastasis initiation. Androgen receptor (AR) has been extensively studied, but its role in relation to breast cancer patient prognosis remains to be clarified. AR/ER ratio has been reported to be an unfavorable prognostic marker in early primary breast cancer, but its role in the patients with advanced disease has to be cleared. We retrospectively analyzed ER, PgR, and AR expression on a case series of 159 specimens of primary BC samples by using immunohistochemistry and 89 patients of these had luminal tumors for which AR and ER expression and survival data were available. For twenty-four patients both primary and metastatic tumors were available. A significantly shorter overall survival was observed in primary tumors with AR/PgR ratio ≥ 1.54 (HR = 2.27; 95% CI 1.30-3.97; p = 0.004). Similarly OS was significantly shorter when ER/PgR ratio ≥2 in primary tumors (HR = 1.89; 95% CI 1.10-3.24; p = 0.021). The analysis of the 24 patients who had biomarker determinations both in primary tumors and metastasis showed a better OS when AR/ER ratio in the metastasis was ≥ 0.90 (p = 0.022). Patients with a high AR/ER ratio in primary tumor that remained high in the metastasis had better prognosis in terms of OS (p = 0.011). Despite we suggested that the ratios AR/ER and AR/PgR could be used to identify patients with different prognosis, their real value needs to be better clarified in different BC settings through prospective studies.

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DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial–Mesenchymal Transition Process

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2019.3504 ◽

2020 ◽

Author(s):

Chang-Rui Liu ◽

Fan-Hua Meng

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Mesenchymal Transition

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Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer

Oncogene ◽

10.1038/s41388-021-01883-6 ◽

2021 ◽

Author(s):

Zhangxiang Zhao ◽

YingYing Guo ◽

Yaoyao Liu ◽

Lichun Sun ◽

Bo Chen ◽

...

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Epithelial Mesenchymal Transition ◽

Expression Profiles ◽

Breast Cancer Subtype ◽

Differential Expression Analysis ◽

Differentially Expressed ◽

Migration And Invasion ◽

Response Analysis ◽

Mesenchymal Transition

AbstractLong non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness of LncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNA PTOV1-AS1 was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation of PTOV1-AS1 could downregulate TJP1 (ZO-1) and E-Cadherin, and upregulate Vimentin, which suggests PTOV1-AS1 may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.

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Nonphosphorylatable PEA15 mutant inhibits epithelial-mesenchymal transition in triple-negative breast cancer partly through the regulation of IL-8 expression

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06316-2 ◽

2021 ◽

Author(s):

Jihyun Park ◽

Moises J. Tacam ◽

Gaurav Chauhan ◽

Evan N. Cohen ◽

Maria Gagliardi ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Lung Metastasis ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Breast Cancer Subtype ◽

Partial Result ◽

Mesenchymal Transition

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks targeted therapies. Patients with TNBC have a very poor prognosis because the disease often metastasizes. New treatment approaches addressing drivers of metastasis and tumor growth are crucial to improving patient outcomes. Developing targeted gene therapy is thus a high priority for TNBC patients. PEA15 (phosphoprotein enriched in astrocytes, 15 kDa) is known to bind to ERK, preventing ERK from being translocated to the nucleus and hence blocking its activity. The biological function of PEA15 is tightly regulated by its phosphorylation at Ser104 and Ser116. However, the function and impact of phosphorylation status of PEA15 in the regulation of TNBC metastasis and in epithelial-to-mesenchymal transition (EMT) are not well understood. Methods We established stable cell lines overexpressing nonphosphorylatable (PEA15-AA) and phospho-mimetic (PEA15-DD) mutants. To dissect specific cellular mechanisms regulated by PEA15 phosphorylation status, we performed RT-PCR immune and metastasis arrays. In vivo mouse models were used to determine the effects of PEA15 phosphorylation on tumor growth and metastasis. Results We found that the nonphosphorylatable mutant PEA15-AA prevented formation of mammospheres and expression of EMT markers in vitro and decreased tumor growth and lung metastasis in in vivo experiments when compared to control, PEA15-WT and phosphomimetic PEA15-DD. However, phosphomimetic mutant PEA15-DD promoted migration, mesenchymal marker expression, tumorigenesis, and lung metastasis in the mouse model. PEA15-AA-mediated inhibition of breast cancer cell migratory capacity and tumorigenesis was the partial result of decreased expression of interleukin-8 (IL-8). Further, we identified that expression of IL-8 was possibly mediated through one of the ERK downstream molecules, Ets-1. Conclusions Our results show that PEA15 phosphorylation status serves as an important regulator for PEA15’s dual role as an oncogene or tumor suppressor and support the potential of PEA15-AA as a therapeutic strategy for treatment of TNBC.

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Extracellular vesicles from MDA-MB-231 breast cancer cells stimulated with insulin-like growth factor 1 mediate an epithelial–mesenchymal transition process in MCF10A mammary epithelial cells

Journal of Cell Communication and Signaling ◽

10.1007/s12079-021-00638-y ◽

2021 ◽

Author(s):

Elizabeth Leal-Orta ◽

Javier Ramirez-Ricardo ◽

Alejandra Garcia-Hernandez ◽

Pedro Cortes-Reynosa ◽

Eduardo Perez Salazar

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Epithelial Cells ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mammary Epithelial Cells ◽

Transition Process ◽

Mammary Epithelial ◽

Mesenchymal Transition

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PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000495900 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2434-2444 ◽

Cited By ~ 14

Author(s):

Deyuan Fu ◽

Chunlan He ◽

Jinli Wei ◽

Zhengquan Zhang ◽

Yulin Luo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Target Therapy ◽

Enzymatic Reaction ◽

Disease Free Survival ◽

Transition Process ◽

Dependent Manner ◽

Poor Overall Survival ◽

Mesenchymal Transition

Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

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