Diffuse and canalicular patterns of glypican‐3 expression reflect malignancy of hepatocellular carcinoma
Glypican‐3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining)....
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| Veröffentlicht in: | Pathology international 2019-03, Vol.69 (3), p.125-134 |
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| creator | Kawaida, Miho Yamazaki, Ken Tsujikawa, Hanako Fukuma, Mariko Abe, Yuta Kitago, Minoru Shinoda, Masahiro Kitagawa, Yuko Sakamoto, Michiie |
| description | Glypican‐3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki‐67 indices, high serum α‐fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT‐activated HCCs. Induction of leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5‐induced cells formed tumors with canaliculus‐like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC. |
| doi_str_mv | 10.1111/pin.12767 |
| format | Article |
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To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki‐67 indices, high serum α‐fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT‐activated HCCs. Induction of leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5‐induced cells formed tumors with canaliculus‐like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.</description><identifier>ISSN: 1320-5463</identifier><identifier>EISSN: 1440-1827</identifier><identifier>DOI: 10.1111/pin.12767</identifier><identifier>PMID: 30729617</identifier><language>eng</language><publisher>Australia: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - analysis ; Carcinogens ; Carcinoma, Hepatocellular - pathology ; Comparative analysis ; Correlation ; Female ; Glypicans - metabolism ; glypican‐3 ; Heparan sulfate proteoglycans ; Hepatocellular carcinoma ; Humans ; immunohistochemistry ; Immunohistochemistry - methods ; Leucine ; Liver cancer ; Liver Neoplasms - pathology ; Male ; Malignancy ; Markers ; Middle Aged ; Proteins ; Signal transduction ; Staining ; Staining and Labeling - methods ; Stem cells ; Wnt protein</subject><ispartof>Pathology international, 2019-03, Vol.69 (3), p.125-134</ispartof><rights>2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd</rights><rights>2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4437-9c5c2efe8854f0da9bd5d2ae67d0b25a5fba8126c025d278c0090a46ddf8f3173</citedby><cites>FETCH-LOGICAL-c4437-9c5c2efe8854f0da9bd5d2ae67d0b25a5fba8126c025d278c0090a46ddf8f3173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpin.12767$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpin.12767$$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/30729617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawaida, Miho</creatorcontrib><creatorcontrib>Yamazaki, Ken</creatorcontrib><creatorcontrib>Tsujikawa, Hanako</creatorcontrib><creatorcontrib>Fukuma, Mariko</creatorcontrib><creatorcontrib>Abe, Yuta</creatorcontrib><creatorcontrib>Kitago, Minoru</creatorcontrib><creatorcontrib>Shinoda, Masahiro</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Sakamoto, Michiie</creatorcontrib><title>Diffuse and canalicular patterns of glypican‐3 expression reflect malignancy of hepatocellular carcinoma</title><title>Pathology international</title><addtitle>Pathol Int</addtitle><description>Glypican‐3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki‐67 indices, high serum α‐fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT‐activated HCCs. Induction of leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5‐induced cells formed tumors with canaliculus‐like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Carcinogens</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Comparative analysis</subject><subject>Correlation</subject><subject>Female</subject><subject>Glypicans - metabolism</subject><subject>glypican‐3</subject><subject>Heparan sulfate proteoglycans</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>immunohistochemistry</subject><subject>Immunohistochemistry - methods</subject><subject>Leucine</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Malignancy</subject><subject>Markers</subject><subject>Middle Aged</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Staining</subject><subject>Staining and Labeling - methods</subject><subject>Stem cells</subject><subject>Wnt protein</subject><issn>1320-5463</issn><issn>1440-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtOwzAUhi0EoqUw8AIoEhNDiu04cTKicqtUAQPMluNLceVcsBtBNh6BZ-RJcJvChhdbx9_5pP8H4BTBKQrnsjX1FGGa0T0wRoTAGOWY7od3gmGckiwZgSPvVxAimmTwEIwSSHGRIToGq2ujdedVxGsZCV5za0RnuYtavl4rV_uo0dHS9q0Jn9-fX0mkPlqnvDdNHTmlrRLrqApby5rXot_QryrsNkJZuxUJ7oSpm4ofgwPNrVcnu3sCXm5vnmf38eLxbj67WsSCkITGhUgFVlrleUo0lLwoZSoxVxmVsMQpT3XJc4QzAXGY01xAWEBOMil1rpOQcALOB2_rmrdO-TVbNZ0LyTzDGJIUkQziQF0MlHCN9yEJa52puOsZgmzTKgutsm2rgT3bGbuyUvKP_K0xAJcD8G6s6v83saf5w6D8AVAGg94</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Kawaida, Miho</creator><creator>Yamazaki, Ken</creator><creator>Tsujikawa, Hanako</creator><creator>Fukuma, Mariko</creator><creator>Abe, Yuta</creator><creator>Kitago, Minoru</creator><creator>Shinoda, Masahiro</creator><creator>Kitagawa, Yuko</creator><creator>Sakamoto, Michiie</creator><general>Wiley Subscription Services, Inc</general><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>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201903</creationdate><title>Diffuse and canalicular patterns of glypican‐3 expression reflect malignancy of hepatocellular carcinoma</title><author>Kawaida, Miho ; Yamazaki, Ken ; Tsujikawa, Hanako ; Fukuma, Mariko ; Abe, Yuta ; Kitago, Minoru ; Shinoda, Masahiro ; Kitagawa, Yuko ; Sakamoto, Michiie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4437-9c5c2efe8854f0da9bd5d2ae67d0b25a5fba8126c025d278c0090a46ddf8f3173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Carcinogens</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Comparative analysis</topic><topic>Correlation</topic><topic>Female</topic><topic>Glypicans - metabolism</topic><topic>glypican‐3</topic><topic>Heparan sulfate proteoglycans</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>immunohistochemistry</topic><topic>Immunohistochemistry - methods</topic><topic>Leucine</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Malignancy</topic><topic>Markers</topic><topic>Middle Aged</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Staining</topic><topic>Staining and Labeling - methods</topic><topic>Stem cells</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawaida, Miho</creatorcontrib><creatorcontrib>Yamazaki, Ken</creatorcontrib><creatorcontrib>Tsujikawa, Hanako</creatorcontrib><creatorcontrib>Fukuma, Mariko</creatorcontrib><creatorcontrib>Abe, Yuta</creatorcontrib><creatorcontrib>Kitago, Minoru</creatorcontrib><creatorcontrib>Shinoda, Masahiro</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Sakamoto, Michiie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Pathology international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawaida, Miho</au><au>Yamazaki, Ken</au><au>Tsujikawa, Hanako</au><au>Fukuma, Mariko</au><au>Abe, Yuta</au><au>Kitago, Minoru</au><au>Shinoda, Masahiro</au><au>Kitagawa, Yuko</au><au>Sakamoto, Michiie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diffuse and canalicular patterns of glypican‐3 expression reflect malignancy of hepatocellular carcinoma</atitle><jtitle>Pathology international</jtitle><addtitle>Pathol Int</addtitle><date>2019-03</date><risdate>2019</risdate><volume>69</volume><issue>3</issue><spage>125</spage><epage>134</epage><pages>125-134</pages><issn>1320-5463</issn><eissn>1440-1827</eissn><abstract>Glypican‐3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki‐67 indices, high serum α‐fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT‐activated HCCs. Induction of leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5‐induced cells formed tumors with canaliculus‐like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.</abstract><cop>Australia</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30729617</pmid><doi>10.1111/pin.12767</doi><tpages>10</tpages></addata></record> |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor - analysis Carcinogens Carcinoma, Hepatocellular - pathology Comparative analysis Correlation Female Glypicans - metabolism glypican‐3 Heparan sulfate proteoglycans Hepatocellular carcinoma Humans immunohistochemistry Immunohistochemistry - methods Leucine Liver cancer Liver Neoplasms - pathology Male Malignancy Markers Middle Aged Proteins Signal transduction Staining Staining and Labeling - methods Stem cells Wnt protein |
| title | Diffuse and canalicular patterns of glypican‐3 expression reflect malignancy of hepatocellular carcinoma |
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