Immunohistochemical study of characteristics of bile duct dysplasia evaluated on the basis of expression of metastasis/invasion‐related factors and p53

Background/Purpose Bile duct carcinoma still continues to have an unfavorable prognosis, despite an improved rate of curative resection and the development of surgical techniques. We evaluated the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and in...

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Veröffentlicht in:Journal of Hepato‐Biliary‐Pancreatic Surgery 2004-12, Vol.11 (6), p.409-416
Hauptverfasser: Chiba, Hideo, Nagai, Hideo, Ohdaira, Takeshi, Yasuda, Yoshikazu, Saito, Ken
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container_issue 6
container_start_page 409
container_title Journal of Hepato‐Biliary‐Pancreatic Surgery
container_volume 11
creator Chiba, Hideo
Nagai, Hideo
Ohdaira, Takeshi
Yasuda, Yoshikazu
Saito, Ken
description Background/Purpose Bile duct carcinoma still continues to have an unfavorable prognosis, despite an improved rate of curative resection and the development of surgical techniques. We evaluated the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and intercellular adhesive factors (E‐cadherin, α‐catenin, β‐catenin) in cancer, dysplastic lesions, and normal (nonatypical) epithelia (glandulous ducts) in patients with bile duct carcinoma. Positivity rates for these factors were compared among the three histological types to examine the characteristics of bile duct dysplasia. Methods Among 89 patients with bile duct carcinoma resected at our hospital during the past 10 years, we studied 18 patients who concurrently had a cancerous lesion, dysplastic lesion, and normal (nonatypical) epithelia adjoining each other in excised specimens. The immunohistochemical expressions of MMPs, TIMPs, E‐cadherin, α‐catenin, and β‐catenin were investigated. Results Positivity rates for MMP‐9, TIMP‐1, TIMP‐2, membrane type (MT) 1‐MMP, MT2‐MMP, and E‐cadherin were significantly higher in cancerous than in normal epithelium. Only the positivity rate for MT1‐MMP was significantly higher in dysplasia than in normal epithelium. Positivity for MMP‐related factors correlated with the degree of atypia of the bile duct epithelium. Differences between cancer and dysplasia were slightly greater than those between dysplasia and normal epithelium. Likelihood ratios between cancer and dysplasia, cancer and normal epithelium, and dysplasia and normal epithelium were higher than 5 for all metastasis‐related factors and higher than 10 for most factors. This finding suggests that a normal‐dysplasia‐carcinoma sequence underlies the development of bile duct cancer accompanied by dysplasia. Conclusions The phenotypic characteristics of dysplasia are closer to those of normal epithelium than to those of cancerous epithelium. A normal‐dysplasia‐carcinoma sequence is apparently involved in the development of bile duct cancer accompanied by dysplastic cells.
doi_str_mv 10.1007/s00534-004-0928-1
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We evaluated the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and intercellular adhesive factors (E‐cadherin, α‐catenin, β‐catenin) in cancer, dysplastic lesions, and normal (nonatypical) epithelia (glandulous ducts) in patients with bile duct carcinoma. Positivity rates for these factors were compared among the three histological types to examine the characteristics of bile duct dysplasia. Methods Among 89 patients with bile duct carcinoma resected at our hospital during the past 10 years, we studied 18 patients who concurrently had a cancerous lesion, dysplastic lesion, and normal (nonatypical) epithelia adjoining each other in excised specimens. The immunohistochemical expressions of MMPs, TIMPs, E‐cadherin, α‐catenin, and β‐catenin were investigated. Results Positivity rates for MMP‐9, TIMP‐1, TIMP‐2, membrane type (MT) 1‐MMP, MT2‐MMP, and E‐cadherin were significantly higher in cancerous than in normal epithelium. Only the positivity rate for MT1‐MMP was significantly higher in dysplasia than in normal epithelium. Positivity for MMP‐related factors correlated with the degree of atypia of the bile duct epithelium. Differences between cancer and dysplasia were slightly greater than those between dysplasia and normal epithelium. Likelihood ratios between cancer and dysplasia, cancer and normal epithelium, and dysplasia and normal epithelium were higher than 5 for all metastasis‐related factors and higher than 10 for most factors. This finding suggests that a normal‐dysplasia‐carcinoma sequence underlies the development of bile duct cancer accompanied by dysplasia. Conclusions The phenotypic characteristics of dysplasia are closer to those of normal epithelium than to those of cancerous epithelium. A normal‐dysplasia‐carcinoma sequence is apparently involved in the development of bile duct cancer accompanied by dysplastic cells.</description><identifier>ISSN: 0944-1166</identifier><identifier>EISSN: 1868-6982</identifier><identifier>EISSN: 1436-0691</identifier><identifier>DOI: 10.1007/s00534-004-0928-1</identifier><identifier>PMID: 15619017</identifier><language>eng</language><publisher>Japan</publisher><subject>bile duct dysplasia ; Bile Duct Neoplasms - metabolism ; Bile Duct Neoplasms - pathology ; Bile Ducts - pathology ; Cell Adhesion Molecules - metabolism ; Humans ; immunohistochemical study ; Immunohistochemistry ; intercellular adhesive factors ; matrix metalloproteinases ; Matrix Metalloproteinases - metabolism ; Neoplasm Invasiveness ; Tissue Inhibitor of Metalloproteinases - metabolism ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>Journal of Hepato‐Biliary‐Pancreatic Surgery, 2004-12, Vol.11 (6), p.409-416</ispartof><rights>2004 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4006-595d326ef23a4eeffe8a7024a4cd71f0bdc389fbab85fcbbc73d3a05211c35c43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1007%2Fs00534-004-0928-1$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1007%2Fs00534-004-0928-1$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15619017$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chiba, Hideo</creatorcontrib><creatorcontrib>Nagai, Hideo</creatorcontrib><creatorcontrib>Ohdaira, Takeshi</creatorcontrib><creatorcontrib>Yasuda, Yoshikazu</creatorcontrib><creatorcontrib>Saito, Ken</creatorcontrib><title>Immunohistochemical study of characteristics of bile duct dysplasia evaluated on the basis of expression of metastasis/invasion‐related factors and p53</title><title>Journal of Hepato‐Biliary‐Pancreatic Surgery</title><addtitle>J Hepatobiliary Pancreat Surg</addtitle><description>Background/Purpose Bile duct carcinoma still continues to have an unfavorable prognosis, despite an improved rate of curative resection and the development of surgical techniques. We evaluated the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and intercellular adhesive factors (E‐cadherin, α‐catenin, β‐catenin) in cancer, dysplastic lesions, and normal (nonatypical) epithelia (glandulous ducts) in patients with bile duct carcinoma. Positivity rates for these factors were compared among the three histological types to examine the characteristics of bile duct dysplasia. Methods Among 89 patients with bile duct carcinoma resected at our hospital during the past 10 years, we studied 18 patients who concurrently had a cancerous lesion, dysplastic lesion, and normal (nonatypical) epithelia adjoining each other in excised specimens. The immunohistochemical expressions of MMPs, TIMPs, E‐cadherin, α‐catenin, and β‐catenin were investigated. Results Positivity rates for MMP‐9, TIMP‐1, TIMP‐2, membrane type (MT) 1‐MMP, MT2‐MMP, and E‐cadherin were significantly higher in cancerous than in normal epithelium. Only the positivity rate for MT1‐MMP was significantly higher in dysplasia than in normal epithelium. Positivity for MMP‐related factors correlated with the degree of atypia of the bile duct epithelium. Differences between cancer and dysplasia were slightly greater than those between dysplasia and normal epithelium. Likelihood ratios between cancer and dysplasia, cancer and normal epithelium, and dysplasia and normal epithelium were higher than 5 for all metastasis‐related factors and higher than 10 for most factors. This finding suggests that a normal‐dysplasia‐carcinoma sequence underlies the development of bile duct cancer accompanied by dysplasia. Conclusions The phenotypic characteristics of dysplasia are closer to those of normal epithelium than to those of cancerous epithelium. A normal‐dysplasia‐carcinoma sequence is apparently involved in the development of bile duct cancer accompanied by dysplastic cells.</description><subject>bile duct dysplasia</subject><subject>Bile Duct Neoplasms - metabolism</subject><subject>Bile Duct Neoplasms - pathology</subject><subject>Bile Ducts - pathology</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Humans</subject><subject>immunohistochemical study</subject><subject>Immunohistochemistry</subject><subject>intercellular adhesive factors</subject><subject>matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0944-1166</issn><issn>1868-6982</issn><issn>1436-0691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1uFDEUhS0EIkvgAWiQK7pJ7LE9nikhAhIUCQqorTv2tdZo_rA9ge14BFpejyeJJ7sSJYVl3XPPOZb8EfKSswvOmL5MjCkhK8bK6eq24o_IjrdNWzVdWz8mO9ZJWXHeNGfkWUrfGONatfopOeOq4V2ZduTPzTiu07wPKc92j2OwMNCUV3egs6d2DxFsxljWwaZN6sOA1K02U3dIywApAMU7GFbI6Og80bxH2hf5wY0_l4gphaKXacQMKW-7yzDdwSb__fU74vCQ9eWlOSYKk6OLEs_JEw9Dwhen-5x8ff_uy9V1dfvpw83Vm9vKSsaaSnXKibpBXwuQiN5jC5rVEqR1mnvWOyvazvfQt8rbvrdaOAFM1ZxboawU5-T1sXeJ8_cVUzZjSBaHASac12QazTvV1boY-dFo45xSRG-WGEaIB8OZ2XiYIw9TeJiNh-El8-pUvvYjun-JE4Bi0EfDj_Kvh_83mo_Xbz9zJhtxD9R5nA4</recordid><startdate>200412</startdate><enddate>200412</enddate><creator>Chiba, Hideo</creator><creator>Nagai, Hideo</creator><creator>Ohdaira, Takeshi</creator><creator>Yasuda, Yoshikazu</creator><creator>Saito, Ken</creator><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>7X8</scope></search><sort><creationdate>200412</creationdate><title>Immunohistochemical study of characteristics of bile duct dysplasia evaluated on the basis of expression of metastasis/invasion‐related factors and p53</title><author>Chiba, Hideo ; Nagai, Hideo ; Ohdaira, Takeshi ; Yasuda, Yoshikazu ; Saito, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4006-595d326ef23a4eeffe8a7024a4cd71f0bdc389fbab85fcbbc73d3a05211c35c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>bile duct dysplasia</topic><topic>Bile Duct Neoplasms - metabolism</topic><topic>Bile Duct Neoplasms - pathology</topic><topic>Bile Ducts - pathology</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Humans</topic><topic>immunohistochemical study</topic><topic>Immunohistochemistry</topic><topic>intercellular adhesive factors</topic><topic>matrix metalloproteinases</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Neoplasm Invasiveness</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiba, Hideo</creatorcontrib><creatorcontrib>Nagai, Hideo</creatorcontrib><creatorcontrib>Ohdaira, Takeshi</creatorcontrib><creatorcontrib>Yasuda, Yoshikazu</creatorcontrib><creatorcontrib>Saito, Ken</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Hepato‐Biliary‐Pancreatic Surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiba, Hideo</au><au>Nagai, Hideo</au><au>Ohdaira, Takeshi</au><au>Yasuda, Yoshikazu</au><au>Saito, Ken</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical study of characteristics of bile duct dysplasia evaluated on the basis of expression of metastasis/invasion‐related factors and p53</atitle><jtitle>Journal of Hepato‐Biliary‐Pancreatic Surgery</jtitle><addtitle>J Hepatobiliary Pancreat Surg</addtitle><date>2004-12</date><risdate>2004</risdate><volume>11</volume><issue>6</issue><spage>409</spage><epage>416</epage><pages>409-416</pages><issn>0944-1166</issn><eissn>1868-6982</eissn><eissn>1436-0691</eissn><abstract>Background/Purpose Bile duct carcinoma still continues to have an unfavorable prognosis, despite an improved rate of curative resection and the development of surgical techniques. We evaluated the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and intercellular adhesive factors (E‐cadherin, α‐catenin, β‐catenin) in cancer, dysplastic lesions, and normal (nonatypical) epithelia (glandulous ducts) in patients with bile duct carcinoma. Positivity rates for these factors were compared among the three histological types to examine the characteristics of bile duct dysplasia. Methods Among 89 patients with bile duct carcinoma resected at our hospital during the past 10 years, we studied 18 patients who concurrently had a cancerous lesion, dysplastic lesion, and normal (nonatypical) epithelia adjoining each other in excised specimens. The immunohistochemical expressions of MMPs, TIMPs, E‐cadherin, α‐catenin, and β‐catenin were investigated. Results Positivity rates for MMP‐9, TIMP‐1, TIMP‐2, membrane type (MT) 1‐MMP, MT2‐MMP, and E‐cadherin were significantly higher in cancerous than in normal epithelium. Only the positivity rate for MT1‐MMP was significantly higher in dysplasia than in normal epithelium. Positivity for MMP‐related factors correlated with the degree of atypia of the bile duct epithelium. Differences between cancer and dysplasia were slightly greater than those between dysplasia and normal epithelium. Likelihood ratios between cancer and dysplasia, cancer and normal epithelium, and dysplasia and normal epithelium were higher than 5 for all metastasis‐related factors and higher than 10 for most factors. This finding suggests that a normal‐dysplasia‐carcinoma sequence underlies the development of bile duct cancer accompanied by dysplasia. Conclusions The phenotypic characteristics of dysplasia are closer to those of normal epithelium than to those of cancerous epithelium. A normal‐dysplasia‐carcinoma sequence is apparently involved in the development of bile duct cancer accompanied by dysplastic cells.</abstract><cop>Japan</cop><pmid>15619017</pmid><doi>10.1007/s00534-004-0928-1</doi><tpages>8</tpages></addata></record>
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subjects bile duct dysplasia
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Bile Ducts - pathology
Cell Adhesion Molecules - metabolism
Humans
immunohistochemical study
Immunohistochemistry
intercellular adhesive factors
matrix metalloproteinases
Matrix Metalloproteinases - metabolism
Neoplasm Invasiveness
Tissue Inhibitor of Metalloproteinases - metabolism
Tumor Suppressor Protein p53 - metabolism
title Immunohistochemical study of characteristics of bile duct dysplasia evaluated on the basis of expression of metastasis/invasion‐related factors and p53
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