Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker
Summary Hepatocyte growth factor has been identified as a lymphangiogenic factor in experimental animal models. However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-...
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| creator | Zhao, Dan, MD Wang, Si-Hua, MD Feng, Yang, MD Hua, Cheng-Ge, MD Zhao, Jun, MD Tang, Xiu-Fa, MD |
| description | Summary Hepatocyte growth factor has been identified as a lymphangiogenic factor in experimental animal models. However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-Met on tumor-related lymphatic vessels remains to be further investigated. Lymphatic vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met , and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma. The distribution of c-Met on lymphatic endothelium was examined. High expression of c-Met in tumor cells was significantly associated with advanced clinical stage ( P = .045), high expression of vascular endothelial growth factor-C ( P < .001), higher peritumoral lymphatic vessel density ( P = .003), higher incidence of peritumoral lymphatic invasion ( P = .032), and positive lymph node status ( P = .005), in spite of its negative expression on most lymphatic vessels. Patients with high– c-Met expression tumors exhibited shorter overall survival and disease-free survival ( P < .001 and P = .010, respectively). Taken together, our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factor, vascular endothelial growth factor C, and, by extension, with lymphangiogenesis and lymph node metastasis, suggesting important prognostic significance of c-Met for patients with oral squamous cell carcinoma. |
| doi_str_mv | 10.1016/j.humpath.2010.03.012 |
| format | Article |
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However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-Met on tumor-related lymphatic vessels remains to be further investigated. Lymphatic vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met , and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma. The distribution of c-Met on lymphatic endothelium was examined. High expression of c-Met in tumor cells was significantly associated with advanced clinical stage ( P = .045), high expression of vascular endothelial growth factor-C ( P < .001), higher peritumoral lymphatic vessel density ( P = .003), higher incidence of peritumoral lymphatic invasion ( P = .032), and positive lymph node status ( P = .005), in spite of its negative expression on most lymphatic vessels. Patients with high– c-Met expression tumors exhibited shorter overall survival and disease-free survival ( P < .001 and P = .010, respectively). Taken together, our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factor, vascular endothelial growth factor C, and, by extension, with lymphangiogenesis and lymph node metastasis, suggesting important prognostic significance of c-Met for patients with oral squamous cell carcinoma.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2010.03.012</identifier><identifier>PMID: 21531000</identifier><identifier>CODEN: HPCQA4</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Biomarkers, Tumor - metabolism ; c-Met ; Carcinoma, Squamous Cell - diagnosis ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Endothelial Cells - metabolism ; Endothelium, Lymphatic - metabolism ; Female ; Hematologic and hematopoietic diseases ; Hepatocyte Growth Factor - metabolism ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymph node metastasis ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels - metabolism ; Lymphatic Vessels - pathology ; Male ; Medical research ; Medical sciences ; Mouth Neoplasms - diagnosis ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; Neoplasm Recurrence, Local ; Oral squamous cell carcinoma ; Otorhinolaryngology. Stomatology ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-met - metabolism ; Rodents ; Studies ; Survival Analysis ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor C - metabolism</subject><ispartof>Human pathology, 2011-10, Vol.42 (10), p.1514-1523</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-c1379414eda522f5d6625aaed7fb3bddcea5c5ecb64af4223491ec2bd15f1f673</citedby><cites>FETCH-LOGICAL-c477t-c1379414eda522f5d6625aaed7fb3bddcea5c5ecb64af4223491ec2bd15f1f673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817711000554$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24613035$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21531000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Dan, MD</creatorcontrib><creatorcontrib>Wang, Si-Hua, MD</creatorcontrib><creatorcontrib>Feng, Yang, MD</creatorcontrib><creatorcontrib>Hua, Cheng-Ge, MD</creatorcontrib><creatorcontrib>Zhao, Jun, MD</creatorcontrib><creatorcontrib>Tang, Xiu-Fa, MD</creatorcontrib><title>Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Hepatocyte growth factor has been identified as a lymphangiogenic factor in experimental animal models. However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-Met on tumor-related lymphatic vessels remains to be further investigated. Lymphatic vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met , and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma. The distribution of c-Met on lymphatic endothelium was examined. High expression of c-Met in tumor cells was significantly associated with advanced clinical stage ( P = .045), high expression of vascular endothelial growth factor-C ( P < .001), higher peritumoral lymphatic vessel density ( P = .003), higher incidence of peritumoral lymphatic invasion ( P = .032), and positive lymph node status ( P = .005), in spite of its negative expression on most lymphatic vessels. Patients with high– c-Met expression tumors exhibited shorter overall survival and disease-free survival ( P < .001 and P = .010, respectively). Taken together, our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factor, vascular endothelial growth factor C, and, by extension, with lymphangiogenesis and lymph node metastasis, suggesting important prognostic significance of c-Met for patients with oral squamous cell carcinoma.</description><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>c-Met</subject><subject>Carcinoma, Squamous Cell - diagnosis</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Lymphatic - metabolism</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymph node metastasis</subject><subject>Lymphangiogenesis</subject><subject>Lymphatic Metastasis</subject><subject>Lymphatic Vessels - metabolism</subject><subject>Lymphatic Vessels - pathology</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Mouth Neoplasms - diagnosis</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - pathology</subject><subject>Neoplasm Recurrence, Local</subject><subject>Oral squamous cell carcinoma</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Rodents</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor C - metabolism</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkt1u1DAQhSMEoqXwCCBLCHHTXWwnTrJcgFDFT6UiLoBra9ae7Hqb2FuP07LPysvgsAtFvUGyZMn-5swZHxfFU8Hngov61Wa-HoctpPVc8nzGyzkX8l5xLFQpZ225kPeLY86retaKpjkqHhFtOBdCVephcSQzJTjnx8XPc58ipHEIEXpmZp8xMfyxjUjkgmeOGBAF4yChZTcurdk1kBl7iAy9DWmNvcuFqxhu8l0HJoXIzv6ROGX9btiuwa9cWKFHcnTKwNv9MfPBIhswAeWVuznPfjuhqxGGMBIz2GdfEI3zYYDXzA3b3hlIWZpYl5uNhNkjA7aNYeUDJWfYAPES4-PiQQc94ZPDflJ8__D-29mn2cWXj-dn7y5mpmqaNDOibBaVqNCCkrJTtq6lAkDbdMtyaa1BUEahWdYVdJWUZbUQaOTSCtWJrm7Kk-LlXjc7uBqRkh4cTb7BYx5BtwvVKiWVyOTzO-QmjNFnc1rwsmrbtq5VptSeMjEQRez0Nro80i5Degpfb_QhfD2Fr3mpc_i57tlBfVwOaP9W_Uk7Ay8OQM4Q-i6CN45uuaoWJS8nA2_3HOZXu3YYNRmH3qB1EU3SNrj_WnlzR8H0zufc-kvcId1OrUlqrr9OP3X6qGLyqVRV_gIxD-uZ</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Zhao, Dan, MD</creator><creator>Wang, Si-Hua, MD</creator><creator>Feng, Yang, MD</creator><creator>Hua, Cheng-Ge, MD</creator><creator>Zhao, Jun, MD</creator><creator>Tang, Xiu-Fa, MD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20111001</creationdate><title>Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker</title><author>Zhao, Dan, MD ; Wang, Si-Hua, MD ; Feng, Yang, MD ; Hua, Cheng-Ge, MD ; Zhao, Jun, MD ; Tang, Xiu-Fa, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-c1379414eda522f5d6625aaed7fb3bddcea5c5ecb64af4223491ec2bd15f1f673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>c-Met</topic><topic>Carcinoma, Squamous Cell - diagnosis</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium, Lymphatic - metabolism</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymph node metastasis</topic><topic>Lymphangiogenesis</topic><topic>Lymphatic Metastasis</topic><topic>Lymphatic Vessels - metabolism</topic><topic>Lymphatic Vessels - pathology</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Mouth Neoplasms - diagnosis</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>Neoplasm Recurrence, Local</topic><topic>Oral squamous cell carcinoma</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Rodents</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor C - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Dan, MD</creatorcontrib><creatorcontrib>Wang, Si-Hua, MD</creatorcontrib><creatorcontrib>Feng, Yang, MD</creatorcontrib><creatorcontrib>Hua, Cheng-Ge, MD</creatorcontrib><creatorcontrib>Zhao, Jun, MD</creatorcontrib><creatorcontrib>Tang, Xiu-Fa, MD</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Dan, MD</au><au>Wang, Si-Hua, MD</au><au>Feng, Yang, MD</au><au>Hua, Cheng-Ge, MD</au><au>Zhao, Jun, MD</au><au>Tang, Xiu-Fa, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>42</volume><issue>10</issue><spage>1514</spage><epage>1523</epage><pages>1514-1523</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>Summary Hepatocyte growth factor has been identified as a lymphangiogenic factor in experimental animal models. However, the correlation between hepatocyte growth factor or c-Met expression and lymphangiogenesis in human spontaneous tumors has been rarely reported, and the distribution pattern of c-Met on tumor-related lymphatic vessels remains to be further investigated. Lymphatic vessel density, lymphatic invasion, the expression of hepatocyte growth factor, c-Met , and vascular endothelial growth factor C proteins were evaluated by immunohistochemistry in 76 cases of oral squamous cell carcinoma. The distribution of c-Met on lymphatic endothelium was examined. High expression of c-Met in tumor cells was significantly associated with advanced clinical stage ( P = .045), high expression of vascular endothelial growth factor-C ( P < .001), higher peritumoral lymphatic vessel density ( P = .003), higher incidence of peritumoral lymphatic invasion ( P = .032), and positive lymph node status ( P = .005), in spite of its negative expression on most lymphatic vessels. Patients with high– c-Met expression tumors exhibited shorter overall survival and disease-free survival ( P < .001 and P = .010, respectively). Taken together, our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factor, vascular endothelial growth factor C, and, by extension, with lymphangiogenesis and lymph node metastasis, suggesting important prognostic significance of c-Met for patients with oral squamous cell carcinoma.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>21531000</pmid><doi>10.1016/j.humpath.2010.03.012</doi><tpages>10</tpages></addata></record> |
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| subjects | Biological and medical sciences Biomarkers, Tumor - metabolism c-Met Carcinoma, Squamous Cell - diagnosis Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Endothelial Cells - metabolism Endothelium, Lymphatic - metabolism Female Hematologic and hematopoietic diseases Hepatocyte Growth Factor - metabolism Humans Investigative techniques, diagnostic techniques (general aspects) Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymph node metastasis Lymphangiogenesis Lymphatic Metastasis Lymphatic Vessels - metabolism Lymphatic Vessels - pathology Male Medical research Medical sciences Mouth Neoplasms - diagnosis Mouth Neoplasms - metabolism Mouth Neoplasms - pathology Neoplasm Recurrence, Local Oral squamous cell carcinoma Otorhinolaryngology. Stomatology Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Prognosis Proteins Proto-Oncogene Proteins c-met - metabolism Rodents Studies Survival Analysis Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology Vascular endothelial growth factor Vascular Endothelial Growth Factor C - metabolism |
| title | Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker |
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