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CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis

CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis. We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor‐infiltrating lymphocytes (TILs), and vascular invasion in bre...

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Autores principales: Chen, Ying, Klingen, Tor Audun, Aas, Hans, Wik, Elisabeth, Akslen, Lars A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073931/
https://www.ncbi.nlm.nih.gov/pubmed/36598153
http://dx.doi.org/10.1002/cjp2.309
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author Chen, Ying
Klingen, Tor Audun
Aas, Hans
Wik, Elisabeth
Akslen, Lars A
author_facet Chen, Ying
Klingen, Tor Audun
Aas, Hans
Wik, Elisabeth
Akslen, Lars A
author_sort Chen, Ying
collection PubMed
description CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis. We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor‐infiltrating lymphocytes (TILs), and vascular invasion in breast cancer. A population‐based series of 282 cases (200 screen detected and 82 interval patients) from the Norwegian Breast Cancer Screening Program was examined. Immunohistochemical staining for CD47 and CD68 was evaluated on tissue microarray (TMA) slides. For CD47 evaluation, a staining index was used. CD68 tumor‐associated macrophages were counted and dichotomized. TIL subsets (CD45, CD3, CD4, CD8, and FOXP3) were counted and dichotomized using immunohistochemistry on TMA slides. Vascular invasion (both lymphatic and blood vessel) was determined on whole tissue slides. High CD47 tumor cell expression or high counts of CD68 macrophages were significantly associated with elevated levels of all TIL subsets (p < 0.02), CD163 macrophages (p < 0.001), blood vessel invasion (CD31 positive) (p < 0.01), and high tumor cell Ki67 (p < 0.004). High CD47 expression was associated with ER negativity (p < 0.001), HER2 positive status (p = 0.03), and interval‐detected tumors (p = 0.03). Combined high expression of CD47–CD68 was associated with a shorter recurrence‐free survival (RFS) by multivariate analysis (hazard ratio [HR]: 2.37, p = 0.018), adjusting for tumor diameter, histologic grade, lymph node status, and molecular subtype. Patients with luminal A tumors showed a shorter RFS for CD47–CD68 high cases by multivariate assessment (HR: 5.73, p = 0.004). This study demonstrates an association of concurrent high CD47 tumor cell expression and high CD68 macrophage counts with various TIL subsets, blood vessel invasion (CD31 positive), other aggressive tumor features, and interval‐presenting breast cancer. Our findings suggest a link between CD47, tumor immune response, and blood vessel invasion (CD31 positive). Combined high expression of CD47–CD68 was an independent prognostic factor associated with poor prognosis in all cases, as well as in the luminal A category.
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spelling pubmed-100739312023-04-06 CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis Chen, Ying Klingen, Tor Audun Aas, Hans Wik, Elisabeth Akslen, Lars A J Pathol Clin Res Original Articles CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis. We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor‐infiltrating lymphocytes (TILs), and vascular invasion in breast cancer. A population‐based series of 282 cases (200 screen detected and 82 interval patients) from the Norwegian Breast Cancer Screening Program was examined. Immunohistochemical staining for CD47 and CD68 was evaluated on tissue microarray (TMA) slides. For CD47 evaluation, a staining index was used. CD68 tumor‐associated macrophages were counted and dichotomized. TIL subsets (CD45, CD3, CD4, CD8, and FOXP3) were counted and dichotomized using immunohistochemistry on TMA slides. Vascular invasion (both lymphatic and blood vessel) was determined on whole tissue slides. High CD47 tumor cell expression or high counts of CD68 macrophages were significantly associated with elevated levels of all TIL subsets (p < 0.02), CD163 macrophages (p < 0.001), blood vessel invasion (CD31 positive) (p < 0.01), and high tumor cell Ki67 (p < 0.004). High CD47 expression was associated with ER negativity (p < 0.001), HER2 positive status (p = 0.03), and interval‐detected tumors (p = 0.03). Combined high expression of CD47–CD68 was associated with a shorter recurrence‐free survival (RFS) by multivariate analysis (hazard ratio [HR]: 2.37, p = 0.018), adjusting for tumor diameter, histologic grade, lymph node status, and molecular subtype. Patients with luminal A tumors showed a shorter RFS for CD47–CD68 high cases by multivariate assessment (HR: 5.73, p = 0.004). This study demonstrates an association of concurrent high CD47 tumor cell expression and high CD68 macrophage counts with various TIL subsets, blood vessel invasion (CD31 positive), other aggressive tumor features, and interval‐presenting breast cancer. Our findings suggest a link between CD47, tumor immune response, and blood vessel invasion (CD31 positive). Combined high expression of CD47–CD68 was an independent prognostic factor associated with poor prognosis in all cases, as well as in the luminal A category. John Wiley & Sons, Inc. 2023-01-04 /pmc/articles/PMC10073931/ /pubmed/36598153 http://dx.doi.org/10.1002/cjp2.309 Text en © 2022 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Chen, Ying
Klingen, Tor Audun
Aas, Hans
Wik, Elisabeth
Akslen, Lars A
CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title_full CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title_fullStr CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title_full_unstemmed CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title_short CD47 and CD68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
title_sort cd47 and cd68 expression in breast cancer is associated with tumor‐infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073931/
https://www.ncbi.nlm.nih.gov/pubmed/36598153
http://dx.doi.org/10.1002/cjp2.309
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