Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases

2021 ◽  
pp. 106689692199071
Author(s):  
Eric Statz ◽  
Julie M. Jorns
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Cytokeratin 7 ◽  
Breast Cancer Metastases ◽  
Her2 Breast Cancer ◽  
Cancer Metastases ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

scholarly journals BSCI-05. HOW MICROGLIA, BRAIN RESIDENT MYELOID CELLS, RESPOND TO BREAST CANCER METASTASIS INTO THE BRAIN?

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Kamil Wojnicki ◽  
Agata Kochalska ◽  
Anna Gieryng ◽  
Tomasz Czernicki ◽  
Ewa Matyja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Triple Negative ◽  
Metastatic Cancer ◽  
Human Breast ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
The Brain ◽  
Metastatic Cancer Cells

Abstract Brain metastasis from different cancers, including lung, breast, melanoma, colorectal or renal cell carcinoma is relatively common and its frequency increases with a prolonged survival of cancer patients. New anti-cancer therapies frequently fail to reduce metastatic burden. While the important role of tumor-associated macrophages as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and potential mechanisms that mediate interactions of cancer cells with brain immune cells - microglia. Triple-negative breast cancer metastases to the brain were discovered in 46% of patients. We evaluated the abundance and morphology of microglia on sections from breast cancer metastases using immunohistochemistry. We found that microglia cells are activated, surround the breast tumor cells and do not infiltrate the solid tumor. Searching for a potential attractant of microglia, we determined osteopontin levels in six human breast cancer cell lines and found upregulation of osteopontin in transformed cells, with the highest level in the triple-negative MDA-MB-231 cells. MDA-MB-231 cells activated primary murine microglia cultures when co-cultured. Invasion of MDA-MB-231 cells in co-cultures with murine immortalized BV2 microglial cells and human SV40 immortalized microglia was increased, as demonstrated using Matrigel Invasion Assay. Using immunofluorescence we detected osteopontin in cancer cells in human breast cancer metastases. Moreover, we found that minocycline, a clinically used antibiotic, reduces the osteopontin production in human breast cancer cells and the most sensitive cells were MDA-MB-231 cells. Our study shows that metastatic cancer cells may employ microglia to facilitate extravasation and colonization of brain parenchyma. We postulate that osteopontin mediates interactions between microglia and metastatic cancer cells and minocycline may interfere with those interactions. Funding: TEAM TECH CORE FACILITY FNP: Development of comprehensive diagnostics and personalized therapy in neuro-oncology

scholarly journals BSCI-04. TARGETING TRIPLE-NEGATIVE BREAST CANCER BRAIN METASTASES WITH A RE-ENGINEERED LUPUS AUTOANTIBODY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i1-i2
Author(s):  
Shenqi Zhang ◽  
Christopher May ◽  
Anupama Shirali ◽  
Valentina Dubljevic ◽  
James Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Nucleoside Transporter ◽  
Cell Nuclei ◽  
Filter Model ◽  
Breast Cancer Brain Metastases ◽  
The Brain

Abstract An unusual lupus anti-DNA autoantibody, 3E10, has potential to be used against triple-negative breast cancer (TNBC) brain metastases. 3E10 penetrates live cell nuclei, inhibits DNA repair, and is selectively toxic to cancer cells with the PTEN and/or DNA-damage response (DDR)-deficiencies that are associated with brain metastases in TNBC. The ENT2 nucleoside transporter that 3E10 uses to cross cell membranes is highly expressed in tumors and in brain endothelial cells (BECs) at the blood-brain barrier (BBB), and 3E10 has previously delivered cargo proteins to ischemic brain in a rat stroke model. We have re-engineered 3E10 into an optimized fragment, called Deoxymab-1 (PAT-DX1), that has increased effect on PTEN/DDR-deficient tumor cells. In the present study we tested the ability of PAT-DX1 to cross the BBB and improve outcomes in a mouse model of TNBC brain metastases. PAT-DX1 crossed from apical to basolateral chambers in an hCMEC/D3 Transwell filter model of the BBB, and penetrated the nuclei of and was toxic to the brain-seeking 231-BR subclone of MDA-MB-231 TNBC cells, which harbors a loss of PTEN compared to parental cells. Brain metastases were generated in nude mice by intracardiac injection of 1.75x105 231-BR cells engineered for expression of luciferase, as confirmed by IVIS one week after injection. Mice with brain metastases were treated by tail vein injection of control (PBS, n=7) or DX1 (20 mg/kg, n=7) 3x/week for 4 weeks. Mice were observed for behavior and weights, and brain radiance efficiency was monitored by weekly IVIS to track metastatic tumor growth. PAT-DX1 significantly suppressed growth of brain metastases based on absolute and relative radiance efficiencies in the brain, increased the median survival of the mice from 38 to 52 days (P< 0.02), and was well tolerated. These results provide proof of concept for use of a re-engineered autoantibody against brain metastases.

scholarly journals Targeted imaging and inhibition of triple-negative breast cancer metastases by a PDGFRβ aptamer

Theranostics ◽  
2018 ◽  
Vol 8 (18) ◽  
pp. 5178-5199 ◽  
Author(s):  
Simona Camorani ◽  
Billy Samuel Hill ◽  
Francesca Collina ◽  
Sara Gargiulo ◽  
Maria Napolitano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Targeted Imaging ◽  
Breast Cancer Metastases ◽  
Cancer Metastases

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

scholarly journals Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Her2 Positive ◽  
Pathway Gene ◽  
Dual Specificity ◽  
The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

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