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GATA-3 expression in breast cancer is related to intratumoral M2 macrophage infiltration and tumor differentiation
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Breast, Endocrine Tumors, and Sarcoma, Karolinska University Hospital, Stockholm, Sweden.
Division of Cell Biology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Department of Breast, Endocrine Tumors, and Sarcoma, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
2023 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 3, article id e0283003Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence indicates that tumor-associated macrophages promote tumor progression and that high macrophage infiltration is correlated with advanced tumor stages and poor prognosis in breast cancer. GATA binding protein 3 (GATA-3) is a differentiation marker related to differentiated states in breast cancer. In this study, we explore how the extent of MI relates to GATA-3 expression, hormonal status, and the differentiation grade of breast cancer. To examine breast cancer in early development, we selected 83 patients that were treated with radical breast-conserving surgery (R0), without lymph node metastases (N0) or distant metastases (M0), with and without postoperative radiotherapy. Immunostaining of M2-macrophage-specific antigen CD163 was used to detect tumor-associated macrophages, and macrophage infiltration was estimated semi-quantitatively into no/low, moderate, and high infiltration. The macrophage infiltration was compared to GATA-3, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression in cancer cells. GATA-3 expression is associated with ER and PR expression but inversely correlated to macrophage infiltration and Nottingham histologic grade. High macrophage infiltration in advanced tumor grade was associated with low GATA-3 expression. The disease-free survival is inversely related to Nottingham histologic grade in patients having tumors with no/low macrophage infiltration, a difference that is not found in patients with moderate/high macrophage infiltration. These findings indicate that macrophage infiltration might impact the differentiation, malignant behavior, and prognosis of breast cancer, regardless of the morphological and hormonal states of the cancer cells in the primary tumor.

Place, publisher, year, edition, pages
Public Library of Science (PLoS) , 2023. Vol. 18, no 3, article id e0283003
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-206662DOI: 10.1371/journal.pone.0283003ISI: 000987433600001PubMedID: 36996051Scopus ID: 2-s2.0-85151409772OAI: oai:DiVA.org:umu-206662DiVA, id: diva2:1751108
Available from: 2023-04-17 Created: 2023-04-17 Last updated: 2023-09-05Bibliographically approved

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Oda, Husam

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