Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer
Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasi...
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| creator | Eiró, Noemí Pidal, Iván Fernandez-Garcia, Belen Junquera, Sara Lamelas, Maria L del Casar, José M González, Luis O López-Muñiz, Alfonso Vizoso, Francisco J |
| description | Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p |
| doi_str_mv | 10.1371/journal.pone.0052796 |
| format | Article |
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The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p<0.01). Therefore, CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0052796</identifier><identifier>PMID: 23300781</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Antibodies ; Antigens ; Antigens, CD - metabolism ; Antigens, CD20 - metabolism ; Antigens, Differentiation, Myelomonocytic - metabolism ; B-Lymphocytes - metabolism ; B-Lymphocytes - pathology ; Biology ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - secondary ; CD20 antigen ; CD3 antigen ; CD3 Complex - metabolism ; Counting ; Disease-Free Survival ; Ethics ; Female ; Gelatinase A ; Genotype & phenotype ; Humans ; Immunohistochemistry ; Immunoreactivity ; Immunotherapy ; Inflammation ; Invasiveness ; Lymphatic system ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Macrophages ; Macrophages - metabolism ; Macrophages - pathology ; Matrix Metalloproteinases, Secreted - metabolism ; Medical prognosis ; Medicine ; Metastases ; Metastasis ; Multivariate Analysis ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Proteases ; Survival ; Survival Analysis ; T cells ; T-Lymphocytes - metabolism ; T-Lymphocytes - pathology ; Tissue Array Analysis ; Tissue inhibitor of metalloproteinase 2 ; Tissue Inhibitor of Metalloproteinase-2 - metabolism ; Tumors ; Womens health</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e52796-e52796</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Eiró et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Eiró et al 2012 Eiró et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-c539d479365f318ec8e3033876c0a08aea30c29318ddc010ffaa70d43c43c2e3</citedby><cites>FETCH-LOGICAL-c659t-c539d479365f318ec8e3033876c0a08aea30c29318ddc010ffaa70d43c43c2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530508/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530508/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23300781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Aziz, Syed A.</contributor><creatorcontrib>Eiró, Noemí</creatorcontrib><creatorcontrib>Pidal, Iván</creatorcontrib><creatorcontrib>Fernandez-Garcia, Belen</creatorcontrib><creatorcontrib>Junquera, Sara</creatorcontrib><creatorcontrib>Lamelas, Maria L</creatorcontrib><creatorcontrib>del Casar, José M</creatorcontrib><creatorcontrib>González, Luis O</creatorcontrib><creatorcontrib>López-Muñiz, Alfonso</creatorcontrib><creatorcontrib>Vizoso, Francisco J</creatorcontrib><title>Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p<0.01). Therefore, CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker.</description><subject>Angiogenesis</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, CD20 - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - pathology</subject><subject>Biology</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - secondary</subject><subject>CD20 antigen</subject><subject>CD3 antigen</subject><subject>CD3 Complex - metabolism</subject><subject>Counting</subject><subject>Disease-Free Survival</subject><subject>Ethics</subject><subject>Female</subject><subject>Gelatinase A</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunoreactivity</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Invasiveness</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eiró, Noemí</au><au>Pidal, Iván</au><au>Fernandez-Garcia, Belen</au><au>Junquera, Sara</au><au>Lamelas, Maria L</au><au>del Casar, José M</au><au>González, Luis O</au><au>López-Muñiz, Alfonso</au><au>Vizoso, Francisco J</au><au>Aziz, Syed A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-26</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e52796</spage><epage>e52796</epage><pages>e52796-e52796</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺), T-cells (CD3⁺ and B-cells (CD20⁺) at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20) ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2). In addition, a high CD68/(CD3+CD20) ratio (>0.05) was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20) ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24), p<0.01). Therefore, CD68/(CD3+CD20) ratio at the invasive front could be used as an important prognostic marker.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23300781</pmid><doi>10.1371/journal.pone.0052796</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e52796-e52796 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327225553 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Angiogenesis Antibodies Antigens Antigens, CD - metabolism Antigens, CD20 - metabolism Antigens, Differentiation, Myelomonocytic - metabolism B-Lymphocytes - metabolism B-Lymphocytes - pathology Biology Biomarkers, Tumor - metabolism Breast cancer Breast carcinoma Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - secondary CD20 antigen CD3 antigen CD3 Complex - metabolism Counting Disease-Free Survival Ethics Female Gelatinase A Genotype & phenotype Humans Immunohistochemistry Immunoreactivity Immunotherapy Inflammation Invasiveness Lymphatic system Lymphocytes Lymphocytes B Lymphocytes T Macrophages Macrophages - metabolism Macrophages - pathology Matrix Metalloproteinases, Secreted - metabolism Medical prognosis Medicine Metastases Metastasis Multivariate Analysis Neoplasm Invasiveness Prognosis Proportional Hazards Models Proteases Survival Survival Analysis T cells T-Lymphocytes - metabolism T-Lymphocytes - pathology Tissue Array Analysis Tissue inhibitor of metalloproteinase 2 Tissue Inhibitor of Metalloproteinase-2 - metabolism Tumors Womens health |
| title | Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer |
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