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Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
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2008 (Engelska)Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, nr 4, s. 780-786Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

Ort, förlag, år, upplaga, sidor
2008. Vol. 123, nr 4, s. 780-786
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-43420DOI: 10.1002/ijc.23527Lokalt ID: 73820OAI: oai:DiVA.org:liu-43420DiVA, id: diva2:264279
Tillgänglig från: 2009-10-10 Skapad: 2009-10-10 Senast uppdaterad: 2017-12-13
Ingår i avhandling
1. Macrophage antigen expression in breast and colorectal cancers: A consequence of macrophage - tumour cell fusion?
Öppna denna publikation i ny flik eller fönster >>Macrophage antigen expression in breast and colorectal cancers: A consequence of macrophage - tumour cell fusion?
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Carcinogenesis is a sophisticated biological process consisting of a series of progressive changes in somatic cells from premalignant to malignant phenotype. Despite the vast information available about cancer cells, the origin of cancer and cause of metastasis still remain enigmatic. The hypothesis of cell fusion is one of several models explaining the evolution of neoplasia into clinically significant cancer. This theory states that cancer cells through heterotypic fusion with host cells generate hybrids expressing traits from both parental cells, and acquire metastatic potentials and growth-promoting properties. The cell fusion theory is still unproven and speculative, but cell fusion is a common biological process in normal tissue. Accumulated evidence shows that macrophage-cancer cell fusion occurs in vitro and in vivo and produces hybrids with metastatic potential, but the clinical significant of cell fusion is unclear. The aim of this thesis is to test this hypothesis in clinical patient materials and to explore the clinical significance of macrophage phenotype traits in solid tumours.

Paraffin-embedded cancer and normal tissue specimens from patients with breast cancer (n=133) and colorectal cancer (two different patient materials with totally 240 patients) were immunostained for the macrophage-specific antigen, CD163. The expression of CD163 was tested in relation to macrophage infiltration and tumour stage, survival time, irradiation, DNA ploidy, cancer cell proliferation and apoptosis.

Phenotypic macrophage traits, such as the expression of CD163, were seen in both breast and colorectal cancers, and were correlated to advanced tumour stages and poor survival. CD163 expression was more frequent in rectal cancer after irradiation and was associated with decreased apoptosis. Cancer cell proliferation was correlated to both macrophage infiltration and CD163 expression. Multivariate analysis showed that CD163 is a significant prognostic factor in both breast and colorectal cancers.

In an attempt to examine factors related to the function of macrophage fusion, the expression of the signalling adaptor protein DAP12 was tested and related to CD163 expression in breast cancers from 133 patients. DAP12 was shown to occur in breast cancer cells and was related to high histologic tumour grade, skeletal and liver metastasis, and poor prognosis. The findings in this thesis support the cell fusion theory and illustrate its clinical impact on tumour progression and metastasis.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2009. s. 67
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1149
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-54820 (URN)978-91-7393-545-6 (ISBN)
Disputation
2009-10-02, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2010-04-14 Skapad: 2010-04-14 Senast uppdaterad: 2010-05-20Bibliografiskt granskad

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