Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met
Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are...
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| Veröffentlicht in: | Cancer science 2014-11, Vol.105 (11), p.1487-1495 |
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| creator | Satoh, Keisuke Nimura, Satoshi Aoki, Mikiko Hamasaki, Makoto Koga, Kaori Iwasaki, Hiroshi Yamashita, Yuichi Kataoka, Hiroaki Nabeshima, Kazuki |
| description | Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c‐Met protein expression and phosphorylation and MET gene copy numbers because c‐Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease‐free survival (DFS) from the low‐grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma.
Our study had two major aims: (1) To evaluate the associations between our scoring system for tumor budding/sprouting, which included budding grade and the proportion of budding‐positive areas, and clinicopathologic factors or prognosis; and (2) To assess the association between c‐Met expression and tumor budding/sprouting. |
| doi_str_mv | 10.1111/cas.12530 |
| format | Article |
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Our study had two major aims: (1) To evaluate the associations between our scoring system for tumor budding/sprouting, which included budding grade and the proportion of budding‐positive areas, and clinicopathologic factors or prognosis; and (2) To assess the association between c‐Met expression and tumor budding/sprouting.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.12530</identifier><identifier>PMID: 25220207</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Angiogenesis ; Cell adhesion & migration ; Cell growth ; Classification ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - surgery ; Cytokeratin ; c‐Met ; Female ; Fibroblasts ; Gene amplification ; Growth factors ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Invasiveness ; Keratins - metabolism ; Male ; Medical prognosis ; MET protein ; Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Original ; Patients ; Phosphorylation ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-met - genetics ; Proto-Oncogene Proteins c-met - metabolism ; Retrospective Studies ; sprouting ; Studies ; tumor budding ; Tumor cells ; tumor invasion ; Tumorigenesis ; Tumors</subject><ispartof>Cancer science, 2014-11, Vol.105 (11), p.1487-1495</ispartof><rights>2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.</rights><rights>2014. This work is published under http://creativecommons.org/licenses/by-nc-nd/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5330-7b0c97d7bfc6d2ea477c75a8cd5c4e3728ca639d52d1336b5362c45aef4088343</citedby><cites>FETCH-LOGICAL-c5330-7b0c97d7bfc6d2ea477c75a8cd5c4e3728ca639d52d1336b5362c45aef4088343</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/PMC4462370/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462370/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25220207$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Satoh, Keisuke</creatorcontrib><creatorcontrib>Nimura, Satoshi</creatorcontrib><creatorcontrib>Aoki, Mikiko</creatorcontrib><creatorcontrib>Hamasaki, Makoto</creatorcontrib><creatorcontrib>Koga, Kaori</creatorcontrib><creatorcontrib>Iwasaki, Hiroshi</creatorcontrib><creatorcontrib>Yamashita, Yuichi</creatorcontrib><creatorcontrib>Kataoka, Hiroaki</creatorcontrib><creatorcontrib>Nabeshima, Kazuki</creatorcontrib><title>Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. 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In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma.
Our study had two major aims: (1) To evaluate the associations between our scoring system for tumor budding/sprouting, which included budding grade and the proportion of budding‐positive areas, and clinicopathologic factors or prognosis; and (2) To assess the association between c‐Met expression and tumor budding/sprouting.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiogenesis</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Classification</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Cytokeratin</subject><subject>c‐Met</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gene amplification</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Invasiveness</subject><subject>Keratins - metabolism</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>MET protein</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Staging</subject><subject>Original</subject><subject>Patients</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-met - genetics</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Retrospective Studies</subject><subject>sprouting</subject><subject>Studies</subject><subject>tumor budding</subject><subject>Tumor cells</subject><subject>tumor invasion</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kd1qFDEYhoMotlYPvAEJeKIH02byM9nxQCiLVqGlgvU4fJN8U1NnkprMrOyRXoLX6JU0262LCoZAAnny8CYvIU9rdliXcWQhH9ZcCXaP7NdCtpVmrLl_u9dVywTfI49yvmJMNLKVD8keV5wzzvQ--X4xjzHRbnbOh0vqA7VxiAntBAO1kKwPcQQKOWOZjnZratdT_IIJpgL7cZxDzBP4sLkOwe1UkBDyK_oh5uy7AYt6FYcVjhgmGntqf_34eYbTY_KghyHjk7v1gHx6--Zi-a46PT95vzw-rawSglW6Y7bVTne9bRxHkFpbrWBhnbISheYLC41oneKuFqLplGi4lQqwl2yxEFIckNdb7_XcjehsSZFgMNfJj5DWJoI3f58E_9lcxpWRsuFCsyJ4cSdI8euMeTKjzxaHAQLGOZu64ZppVX61oM__Qa_inEJ5nuG8ZbWUrdokermlbCpflLDfhamZ2dRqSq3mttbCPvsz_Y783WMBjrbANz_g-v8mszz-uFXeAPVNr6I</recordid><startdate>201411</startdate><enddate>201411</enddate><creator>Satoh, Keisuke</creator><creator>Nimura, Satoshi</creator><creator>Aoki, Mikiko</creator><creator>Hamasaki, Makoto</creator><creator>Koga, Kaori</creator><creator>Iwasaki, Hiroshi</creator><creator>Yamashita, Yuichi</creator><creator>Kataoka, Hiroaki</creator><creator>Nabeshima, Kazuki</creator><general>John Wiley & Sons, Inc</general><general>Blackwell Publishing Ltd</general><scope>24P</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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201411</creationdate><title>Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met</title><author>Satoh, Keisuke ; 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Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c‐Met protein expression and phosphorylation and MET gene copy numbers because c‐Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease‐free survival (DFS) from the low‐grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma.
Our study had two major aims: (1) To evaluate the associations between our scoring system for tumor budding/sprouting, which included budding grade and the proportion of budding‐positive areas, and clinicopathologic factors or prognosis; and (2) To assess the association between c‐Met expression and tumor budding/sprouting.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>25220207</pmid><doi>10.1111/cas.12530</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2014-11, Vol.105 (11), p.1487-1495 |
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| subjects | Adult Aged Aged, 80 and over Angiogenesis Cell adhesion & migration Cell growth Classification Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Colorectal Neoplasms - surgery Cytokeratin c‐Met Female Fibroblasts Gene amplification Growth factors Humans Immunohistochemistry In Situ Hybridization, Fluorescence Invasiveness Keratins - metabolism Male Medical prognosis MET protein Metastasis Middle Aged Neoplasm Grading Neoplasm Metastasis Neoplasm Staging Original Patients Phosphorylation Prognosis Proteins Proto-Oncogene Proteins c-met - genetics Proto-Oncogene Proteins c-met - metabolism Retrospective Studies sprouting Studies tumor budding Tumor cells tumor invasion Tumorigenesis Tumors |
| title | Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met |
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