Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts
Summary Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical re...
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| Veröffentlicht in: | Human pathology 2008-05, Vol.39 (5), p.710-719 |
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| creator | Itatsu, Keita, MD Zen, Yoh, MD Yamaguchi, Junpei, MD Ohira, Shusaku, MD Ishikawa, Akira, MD Ikeda, Hiroko, MD Sato, Yasunori, MD Harada, Kenichi, MD Sasaki, Motoko, MD Sasaki, Masatoshi, MD Sakamoto, Hiroya, MD Nagino, Masato, MD Nimura, Yuji, MD Ohta, Tetsuo, MD Nakanuma, Yasuni, MD, PhD |
| description | Summary Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis. |
| doi_str_mv | 10.1016/j.humpath.2007.09.016 |
| format | Article |
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In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2007.09.016</identifier><identifier>PMID: 18329694</identifier><identifier>CODEN: HPCQA4</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms - diagnosis ; Bile Duct Neoplasms - physiopathology ; Bile ducts ; Bile Ducts, Extrahepatic - pathology ; Bile Ducts, Intrahepatic - pathology ; Biological and medical sciences ; Cell adhesion & migration ; Cholangiocarcinoma ; Cholangiocarcinoma - diagnosis ; Cholangiocarcinoma - physiopathology ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Genotype & phenotype ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 14 - biosynthesis ; Matrix Metalloproteinase 2 - biosynthesis ; Matrix Metalloproteinase 7 - biosynthesis ; Medical sciences ; Middle Aged ; Multivariate analysis ; Papillary carcinoma ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Postoperative Period ; Prognosis ; Surgery ; Survival analysis ; Tumor stage ; Tumors</subject><ispartof>Human pathology, 2008-05, Vol.39 (5), p.710-719</ispartof><rights>2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Limited May 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-2dda75851778208888fab5dbe7579db121beb10862e3847ff4c54035f633852e3</citedby><cites>FETCH-LOGICAL-c391t-2dda75851778208888fab5dbe7579db121beb10862e3847ff4c54035f633852e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.humpath.2007.09.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20349403$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18329694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Itatsu, Keita, MD</creatorcontrib><creatorcontrib>Zen, Yoh, MD</creatorcontrib><creatorcontrib>Yamaguchi, Junpei, MD</creatorcontrib><creatorcontrib>Ohira, Shusaku, MD</creatorcontrib><creatorcontrib>Ishikawa, Akira, MD</creatorcontrib><creatorcontrib>Ikeda, Hiroko, MD</creatorcontrib><creatorcontrib>Sato, Yasunori, MD</creatorcontrib><creatorcontrib>Harada, Kenichi, MD</creatorcontrib><creatorcontrib>Sasaki, Motoko, MD</creatorcontrib><creatorcontrib>Sasaki, Masatoshi, MD</creatorcontrib><creatorcontrib>Sakamoto, Hiroya, MD</creatorcontrib><creatorcontrib>Nagino, Masato, MD</creatorcontrib><creatorcontrib>Nimura, Yuji, MD</creatorcontrib><creatorcontrib>Ohta, Tetsuo, MD</creatorcontrib><creatorcontrib>Nakanuma, Yasuni, MD, PhD</creatorcontrib><title>Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Bile Duct Neoplasms - diagnosis</subject><subject>Bile Duct Neoplasms - physiopathology</subject><subject>Bile ducts</subject><subject>Bile Ducts, Extrahepatic - pathology</subject><subject>Bile Ducts, Intrahepatic - pathology</subject><subject>Biological and medical sciences</subject><subject>Cell adhesion & migration</subject><subject>Cholangiocarcinoma</subject><subject>Cholangiocarcinoma - diagnosis</subject><subject>Cholangiocarcinoma - physiopathology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 14 - biosynthesis</subject><subject>Matrix Metalloproteinase 2 - biosynthesis</subject><subject>Matrix Metalloproteinase 7 - biosynthesis</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Papillary carcinoma</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Postoperative Period</subject><subject>Prognosis</subject><subject>Surgery</subject><subject>Survival analysis</subject><subject>Tumor stage</subject><subject>Tumors</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl2L1DAUhoMo7jj6E5SA6JUzJmnTj5sVWdYPWPBCvQ5perrN2CY1SYfZH-T_9JQpLuyNuTnk8JyPN28IecnZnjNevD_s-3mcdOr3grFyz-o9Zh-RDZeZ2FVZLR6TDWN5sat4WV6QZzEeGONc5vIpueBVJuqizjfkz_VpChCj9Y76jo46BXuiIyQ9DH4KPoF1OgItqY1UOzq7Th990M0AdPIx-QmCTvaIt-BvHWasoZ02yQdqHTW9H7S7td7oYKzzo16mpB5xCLa3gw7v6Bq0aymcUtA9oC5s01gc0s4mxefkSaeHCC_WuCU_P13_uPqyu_n2-evVx5udyWqedqJtdSkriYorwSo8nW5k20Apy7ptuOANNJxVhYCsysuuy43MWSa7IssqickteXvui2J-zxCTGm00MKAG8HNURc3zQlQCwdcPwIOfg8PdFGdZXpV5jUZsiTxTJvgYA3RqCnbU4Q4htbioDmp1US0uKlYrzGLdq7X73IzQ3lettiHwZgV0NHrognbGxn-cwBVqFIbchzMH-GhHC0FFY8EZaG0Ak1Tr7X9XuXzQwQzWWRz6C-4g3qtWUSimvi9fbvlxrGRMcp5nfwEn6dWQ</recordid><startdate>200805</startdate><enddate>200805</enddate><creator>Itatsu, Keita, MD</creator><creator>Zen, Yoh, MD</creator><creator>Yamaguchi, Junpei, MD</creator><creator>Ohira, Shusaku, MD</creator><creator>Ishikawa, Akira, MD</creator><creator>Ikeda, Hiroko, MD</creator><creator>Sato, Yasunori, MD</creator><creator>Harada, Kenichi, MD</creator><creator>Sasaki, Motoko, MD</creator><creator>Sasaki, Masatoshi, MD</creator><creator>Sakamoto, Hiroya, MD</creator><creator>Nagino, Masato, MD</creator><creator>Nimura, Yuji, MD</creator><creator>Ohta, Tetsuo, MD</creator><creator>Nakanuma, Yasuni, MD, PhD</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>200805</creationdate><title>Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts</title><author>Itatsu, Keita, MD ; Zen, Yoh, MD ; Yamaguchi, Junpei, MD ; Ohira, Shusaku, MD ; Ishikawa, Akira, MD ; Ikeda, Hiroko, MD ; Sato, Yasunori, MD ; Harada, Kenichi, MD ; Sasaki, Motoko, MD ; Sasaki, Masatoshi, MD ; Sakamoto, Hiroya, MD ; Nagino, Masato, MD ; Nimura, Yuji, MD ; Ohta, Tetsuo, MD ; Nakanuma, Yasuni, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-2dda75851778208888fab5dbe7579db121beb10862e3847ff4c54035f633852e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Bile Duct Neoplasms - diagnosis</topic><topic>Bile Duct Neoplasms - physiopathology</topic><topic>Bile ducts</topic><topic>Bile Ducts, Extrahepatic - pathology</topic><topic>Bile Ducts, Intrahepatic - pathology</topic><topic>Biological and medical sciences</topic><topic>Cell adhesion & migration</topic><topic>Cholangiocarcinoma</topic><topic>Cholangiocarcinoma - diagnosis</topic><topic>Cholangiocarcinoma - physiopathology</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 14 - biosynthesis</topic><topic>Matrix Metalloproteinase 2 - biosynthesis</topic><topic>Matrix Metalloproteinase 7 - biosynthesis</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Papillary carcinoma</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Postoperative Period</topic><topic>Prognosis</topic><topic>Surgery</topic><topic>Survival analysis</topic><topic>Tumor stage</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Itatsu, Keita, MD</creatorcontrib><creatorcontrib>Zen, Yoh, MD</creatorcontrib><creatorcontrib>Yamaguchi, Junpei, MD</creatorcontrib><creatorcontrib>Ohira, Shusaku, MD</creatorcontrib><creatorcontrib>Ishikawa, Akira, MD</creatorcontrib><creatorcontrib>Ikeda, Hiroko, MD</creatorcontrib><creatorcontrib>Sato, Yasunori, MD</creatorcontrib><creatorcontrib>Harada, Kenichi, MD</creatorcontrib><creatorcontrib>Sasaki, Motoko, MD</creatorcontrib><creatorcontrib>Sasaki, Masatoshi, MD</creatorcontrib><creatorcontrib>Sakamoto, Hiroya, MD</creatorcontrib><creatorcontrib>Nagino, Masato, MD</creatorcontrib><creatorcontrib>Nimura, Yuji, MD</creatorcontrib><creatorcontrib>Ohta, Tetsuo, MD</creatorcontrib><creatorcontrib>Nakanuma, Yasuni, MD, PhD</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>Itatsu, Keita, MD</au><au>Zen, Yoh, MD</au><au>Yamaguchi, Junpei, MD</au><au>Ohira, Shusaku, MD</au><au>Ishikawa, Akira, MD</au><au>Ikeda, Hiroko, MD</au><au>Sato, Yasunori, MD</au><au>Harada, Kenichi, MD</au><au>Sasaki, Motoko, MD</au><au>Sasaki, Masatoshi, MD</au><au>Sakamoto, Hiroya, MD</au><au>Nagino, Masato, MD</au><au>Nimura, Yuji, MD</au><au>Ohta, Tetsuo, MD</au><au>Nakanuma, Yasuni, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2008-05</date><risdate>2008</risdate><volume>39</volume><issue>5</issue><spage>710</spage><epage>719</epage><pages>710-719</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>Summary Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts (collectively referred to as the large bile ducts) is an intractable disease, and a papillary phenotype and well-differentiated histologic grade have been proposed as indicators of a favorable prognosis after surgical resection. In this study, we examined the significance of matrix metalloproteinases (MMPs) in cholangiocarcinoma with respect to clinicopathologic features. We subjected 66 surgically resected specimens of cholangiocarcinoma of the large bile ducts to clinicopathologic examination, including postoperative survival, papillary phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type 1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs, whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9 (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary) cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated with the nonpapillary phenotype, poorly differentiated histologic grade, perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2 and -9 was not associated with any of the clinicopathologic features. Univariate analysis of disease-specific survival revealed that a papillary phenotype and expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to TNM stage, poorly differentiated histologic grade, perineural invasion, and microscopic margin status. Multivariate analysis showed only TNM stage to be an independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an unfavorable postoperative prognostic factor of cholangiocarcinoma arising from the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma might be associated with a favorable prognosis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18329694</pmid><doi>10.1016/j.humpath.2007.09.016</doi><tpages>10</tpages></addata></record> |
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| ispartof | Human pathology, 2008-05, Vol.39 (5), p.710-719 |
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| subjects | Adult Aged Aged, 80 and over Bile Duct Neoplasms - diagnosis Bile Duct Neoplasms - physiopathology Bile ducts Bile Ducts, Extrahepatic - pathology Bile Ducts, Intrahepatic - pathology Biological and medical sciences Cell adhesion & migration Cholangiocarcinoma Cholangiocarcinoma - diagnosis Cholangiocarcinoma - physiopathology Female Gastroenterology. Liver. Pancreas. Abdomen Genotype & phenotype Humans Investigative techniques, diagnostic techniques (general aspects) Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Matrix metalloproteinase Matrix Metalloproteinase 14 - biosynthesis Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 7 - biosynthesis Medical sciences Middle Aged Multivariate analysis Papillary carcinoma Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Postoperative Period Prognosis Surgery Survival analysis Tumor stage Tumors |
| title | Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts |
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