Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis
Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 se...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.3233/ACP-2011-0002 |
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| author | Aula Ammar Rabab A. A. Mohammed Marko Salmi Michael Pepper Emma C. Paish Ian O. Ellis Stewart G. Martin |
| author_facet | Aula Ammar Rabab A. A. Mohammed Marko Salmi Michael Pepper Emma C. Paish Ian O. Ellis Stewart G. Martin |
| author_sort | Aula Ammar |
| collection | DOAJ |
| description | Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, M&phis;). in vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in M&phis;/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with M&phis; indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004). Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN. |
| format | Article |
| id | doaj-art-04262e6fb4d54f0fbb195fc83cb845ee |
| institution | OA Journals |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-04262e6fb4d54f0fbb195fc83cb845ee2025-08-20T02:03:05ZengWileyAnalytical Cellular Pathology2210-71772210-71852011-01-01341-2677810.3233/ACP-2011-0002Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node MetastasisAula Ammar0Rabab A. A. Mohammed1Marko Salmi2Michael Pepper3Emma C. Paish4Ian O. Ellis5Stewart G. Martin6Department of Clinical Oncology, University of Nottingham, Nottingham, UKDepartment of Clinical Oncology, University of Nottingham, Nottingham, UKMediCity Research Laboratory, Turku University, and Department of Bacterial and Inflammatory Diseases, National Public Health Institute, Turku, FinlandUnit for Advanced Studies, University of Pretoria, Lynnwood, South AfricaDepartment of Histopathology, University of Nottingham, Nottingham, UKDepartment of Histopathology, University of Nottingham, Nottingham, UKDepartment of Clinical Oncology, University of Nottingham, Nottingham, UKBackground: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, M&phis;). in vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in M&phis;/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with M&phis; indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004). Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.http://dx.doi.org/10.3233/ACP-2011-0002 |
| spellingShingle | Aula Ammar Rabab A. A. Mohammed Marko Salmi Michael Pepper Emma C. Paish Ian O. Ellis Stewart G. Martin Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis Analytical Cellular Pathology |
| title | Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis |
| title_full | Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis |
| title_fullStr | Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis |
| title_full_unstemmed | Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis |
| title_short | Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis |
| title_sort | lymphatic expression of clever 1 in breast cancer and its relationship with lymph node metastasis |
| url | http://dx.doi.org/10.3233/ACP-2011-0002 |
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