Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could iden...

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Autores principales:	Nazia Riaz, Samantha Burugu, Angela S. Cheng, Samuel C. Y. Leung, Dongxia Gao, Torsten O. Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colony-stimulating factor-1 receptor immunohistochemistry prognosis estrogen receptor-positive breast cancer invasive breast cancer immune check points Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/abeea43bae854238ba522f7fc6b26fb2
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spelling	oai:doaj.org-article:abeea43bae854238ba522f7fc6b26fb22021-11-25T17:03:47ZPrognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer10.3390/cancers132257692072-6694https://doaj.org/article/abeea43bae854238ba522f7fc6b26fb22021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5769https://doaj.org/toc/2072-6694Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of <i>CSF1R</i> mRNA with immune infiltrates and prognosis. Following a prespecified training–validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between <i>CSF1R</i> mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.Nazia RiazSamantha BuruguAngela S. ChengSamuel C. Y. LeungDongxia GaoTorsten O. NielsenMDPI AGarticlecolony-stimulating factor-1 receptorimmunohistochemistryprognosisestrogen receptor-positive breast cancerinvasive breast cancerimmune check pointsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5769, p 5769 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colony-stimulating factor-1 receptor immunohistochemistry prognosis estrogen receptor-positive breast cancer invasive breast cancer immune check points Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colony-stimulating factor-1 receptor immunohistochemistry prognosis estrogen receptor-positive breast cancer invasive breast cancer immune check points Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nazia Riaz Samantha Burugu Angela S. Cheng Samuel C. Y. Leung Dongxia Gao Torsten O. Nielsen Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
description	Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of <i>CSF1R</i> mRNA with immune infiltrates and prognosis. Following a prespecified training–validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between <i>CSF1R</i> mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.
format	article
author	Nazia Riaz Samantha Burugu Angela S. Cheng Samuel C. Y. Leung Dongxia Gao Torsten O. Nielsen
author_facet	Nazia Riaz Samantha Burugu Angela S. Cheng Samuel C. Y. Leung Dongxia Gao Torsten O. Nielsen
author_sort	Nazia Riaz
title	Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
title_short	Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
title_full	Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
title_fullStr	Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
title_full_unstemmed	Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer
title_sort	prognostic significance of csf-1r expression in early invasive breast cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/abeea43bae854238ba522f7fc6b26fb2
work_keys_str_mv	AT naziariaz prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer AT samanthaburugu prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer AT angelascheng prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer AT samuelcyleung prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer AT dongxiagao prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer AT torstenonielsen prognosticsignificanceofcsf1rexpressioninearlyinvasivebreastcancer
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Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer

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