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Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
Umea Univ, Sweden.
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2019 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 475, no 2, p. 151-162Article in journal (Refereed) Published
Abstract [en]

Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non-metastatic invasive BC treated with breast conserving surgery, with and without postoperative radiotherapy (RT). Immunostaining of M2-macrophage-specific antigen CD163 in cancer cells and MI were evaluated, together with ER, PR, HER2, and Ki-67-expression in cancer cells. The tumors were classified into intrinsic subtypes according to the ESMO guidelines. The immunostaining of these markers, MI, and clinical data were analyzed in relation to ipsilateral local recurrence (ILR) as well as recurrence-free (RFS) and disease-free specific (DFS) survival. BC intrinsic subtypes are associated with T-stage, Nottingham Histologic Grade (NHG), and MI. Macrophage phenotype in cancer cells is significantly associated with NHG3-tumors. Significant differences in macrophage infiltration were observed among the intrinsic subtypes of pT1-T2 stage BC. Shorter RFS was observed in luminal B HER2neg tumors after RT, suggesting that this phenotype may be more resistant to irradiation. Ki-67-expression was significantly higher in NHG3 and CD163-positive tumors, as well as those with moderate and high MI. Cancer cell ER expression is inversely related to MI and thus might affect the clinical staging and assessment of BC.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 475, no 2, p. 151-162
Keywords [en]
Breast cancer; Macrophage; CD163; Ki-67; Radiotherapy; Intrinsic subtypes
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-161202DOI: 10.1007/s00428-019-02563-3ISI: 000488315100003PubMedID: 30915533OAI: oai:DiVA.org:liu-161202DiVA, id: diva2:1365674
Note

Funding Agencies|FoU grants from County Council of Ostergotland; Swedish Medical Society

Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-12-10

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Garvin, StinaVikhe Patil, EvaArnesson, Lars-GunnarLindström, Annelie
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Divison of NeurobiologyFaculty of Medicine and Health SciencesClinical pathologyDivision of Surgery, Orthopedics and OncologyDivision of Clinical SciencesDepartment of Surgery in LinköpingDivision of Cell Biology
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