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The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours
In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal–epithelial interactions in these tumours by ex...
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| Published in: | The Journal of pathology 2002-04, Vol.196 (4), p.437-444 |
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| creator | Sawyer, Elinor J. Hanby, Andrew M. Rowan, Andrew J. Gillett, Cheryl E. Thomas, Rachel E. Poulsom, Richard Lakhani, Sunil R. Ellis, Ian O. Ellis, Paul Tomlinson, Ian P. M. |
| description | In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal–epithelial interactions in these tumours by examining the Wnt–APC–β‐catenin pathway. β‐catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty‐six (72%) showed stromal nuclear β‐catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p |
| doi_str_mv | 10.1002/path.1067 |
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M.</creator><creatorcontrib>Sawyer, Elinor J. ; Hanby, Andrew M. ; Rowan, Andrew J. ; Gillett, Cheryl E. ; Thomas, Rachel E. ; Poulsom, Richard ; Lakhani, Sunil R. ; Ellis, Ian O. ; Ellis, Paul ; Tomlinson, Ian P. M.</creatorcontrib><description>In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal–epithelial interactions in these tumours by examining the Wnt–APC–β‐catenin pathway. β‐catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty‐six (72%) showed stromal nuclear β‐catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear β‐catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal β‐catenin staining (p<0.05). Forty‐five of the tumours, including two malignant lesions, were screened for β‐catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different β‐catenin staining patterns. There was an association between strong nuclear β‐catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours. Copyright © 2002 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.1067</identifier><identifier>PMID: 11920740</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>APC ; beta Catenin ; Biological and medical sciences ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; cyclin D1 ; Cyclin D1 - metabolism ; Cytoskeletal Proteins - metabolism ; Disease Progression ; epithelial-stromal interactions ; Epithelium - pathology ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Immunoenzyme Techniques ; Loss of Heterozygosity ; Mammary gland diseases ; Medical sciences ; Neoplasm Proteins - metabolism ; phyllodes ; Phyllodes Tumor - metabolism ; Phyllodes Tumor - pathology ; Proto-Oncogene Proteins - metabolism ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; Stromal Cells - pathology ; Trans-Activators ; Tumors ; Wnt ; Wnt Proteins ; Wnt2 Protein ; Zebrafish Proteins ; β-catenin</subject><ispartof>The Journal of pathology, 2002-04, Vol.196 (4), p.437-444</ispartof><rights>Copyright © 2002 John Wiley & Sons, Ltd.</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2002 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4207-1f23cad8aa222fbf58a1f76b2ef68c6e0aba692a5f62ad2b162f9c27146883e83</citedby><cites>FETCH-LOGICAL-c4207-1f23cad8aa222fbf58a1f76b2ef68c6e0aba692a5f62ad2b162f9c27146883e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.1067$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.1067$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13560146$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11920740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sawyer, Elinor J.</creatorcontrib><creatorcontrib>Hanby, Andrew M.</creatorcontrib><creatorcontrib>Rowan, Andrew J.</creatorcontrib><creatorcontrib>Gillett, Cheryl E.</creatorcontrib><creatorcontrib>Thomas, Rachel E.</creatorcontrib><creatorcontrib>Poulsom, Richard</creatorcontrib><creatorcontrib>Lakhani, Sunil R.</creatorcontrib><creatorcontrib>Ellis, Ian O.</creatorcontrib><creatorcontrib>Ellis, Paul</creatorcontrib><creatorcontrib>Tomlinson, Ian P. M.</creatorcontrib><title>The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal–epithelial interactions in these tumours by examining the Wnt–APC–β‐catenin pathway. β‐catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty‐six (72%) showed stromal nuclear β‐catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear β‐catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal β‐catenin staining (p<0.05). Forty‐five of the tumours, including two malignant lesions, were screened for β‐catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different β‐catenin staining patterns. There was an association between strong nuclear β‐catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours. Copyright © 2002 John Wiley & Sons, Ltd.</description><subject>APC</subject><subject>beta Catenin</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>cyclin D1</subject><subject>Cyclin D1 - metabolism</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Disease Progression</subject><subject>epithelial-stromal interactions</subject><subject>Epithelium - pathology</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Loss of Heterozygosity</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Neoplasm Proteins - metabolism</subject><subject>phyllodes</subject><subject>Phyllodes Tumor - metabolism</subject><subject>Phyllodes Tumor - pathology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>Stromal Cells - pathology</subject><subject>Trans-Activators</subject><subject>Tumors</subject><subject>Wnt</subject><subject>Wnt Proteins</subject><subject>Wnt2 Protein</subject><subject>Zebrafish Proteins</subject><subject>β-catenin</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNqFkEFv1DAUhC0EotvCgT-AcgGpUtPaTuw4x2pFW1BVWGnRHs2LY3cNTrK1HbX773G0ET2hnmx5vpn3PAh9IPicYEwvdhC36carV2hBcM3zWtT8NVokjeZFSaojdBzCb4xxXTP2Fh0RUlNclXiBfq23Otv0MZsyHmF_lumdjVvtLLg8RD904DLbR-1BRTv04SyDvs3Sq73vYfL54d7rEJKWuGy33Ts3tDpkceyG0Yd36I0BF_T7-TxBP6--rJc3-e3366_Ly9tclWmVnBhaKGgFAKXUNIYJIKbiDdWGC8U1hgZ4TYEZTqGlDeHU1IpWpORCFFoUJ-jzITct9DDqEGVng9LOQa-HMciKMEZYxV4EiShESSlO4OkBVH4IwWsjd9524PeSYDn1LqfO5NR7Yj_OoWPT6faZnItOwKcZgKDAGQ-9suGZKxjH6S-Juzhwj9bp_f8nyh-X65t5dH5w2BD10z8H-D8yqRWTm7truVmtl3erb0Kuir8B_qrk</recordid><startdate>200204</startdate><enddate>200204</enddate><creator>Sawyer, Elinor J.</creator><creator>Hanby, Andrew M.</creator><creator>Rowan, Andrew J.</creator><creator>Gillett, Cheryl E.</creator><creator>Thomas, Rachel E.</creator><creator>Poulsom, Richard</creator><creator>Lakhani, Sunil R.</creator><creator>Ellis, Ian O.</creator><creator>Ellis, Paul</creator><creator>Tomlinson, Ian P. M.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200204</creationdate><title>The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours</title><author>Sawyer, Elinor J. ; Hanby, Andrew M. ; Rowan, Andrew J. ; Gillett, Cheryl E. ; Thomas, Rachel E. ; Poulsom, Richard ; Lakhani, Sunil R. ; Ellis, Ian O. ; Ellis, Paul ; Tomlinson, Ian P. 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Obstetrics</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Loss of Heterozygosity</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Neoplasm Proteins - metabolism</topic><topic>phyllodes</topic><topic>Phyllodes Tumor - metabolism</topic><topic>Phyllodes Tumor - pathology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>Stromal Cells - pathology</topic><topic>Trans-Activators</topic><topic>Tumors</topic><topic>Wnt</topic><topic>Wnt Proteins</topic><topic>Wnt2 Protein</topic><topic>Zebrafish Proteins</topic><topic>β-catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawyer, Elinor J.</creatorcontrib><creatorcontrib>Hanby, Andrew M.</creatorcontrib><creatorcontrib>Rowan, Andrew J.</creatorcontrib><creatorcontrib>Gillett, Cheryl E.</creatorcontrib><creatorcontrib>Thomas, Rachel E.</creatorcontrib><creatorcontrib>Poulsom, Richard</creatorcontrib><creatorcontrib>Lakhani, Sunil R.</creatorcontrib><creatorcontrib>Ellis, Ian O.</creatorcontrib><creatorcontrib>Ellis, Paul</creatorcontrib><creatorcontrib>Tomlinson, Ian P. M.</creatorcontrib><collection>Istex</collection><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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawyer, Elinor J.</au><au>Hanby, Andrew M.</au><au>Rowan, Andrew J.</au><au>Gillett, Cheryl E.</au><au>Thomas, Rachel E.</au><au>Poulsom, Richard</au><au>Lakhani, Sunil R.</au><au>Ellis, Ian O.</au><au>Ellis, Paul</au><au>Tomlinson, Ian P. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2002-04</date><risdate>2002</risdate><volume>196</volume><issue>4</issue><spage>437</spage><epage>444</epage><pages>437-444</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><notes>ark:/67375/WNG-WQTCNQJ8-Q</notes><notes>ArticleID:PATH1067</notes><notes>Imperial Cancer Research Fund</notes><notes>istex:85C1E8E803CEAE775C41B6CED66B056B53F3F9CE</notes><notes>Special Trustees of Guy's & St Thomas' Hospital</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal–epithelial interactions in these tumours by examining the Wnt–APC–β‐catenin pathway. β‐catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty‐six (72%) showed stromal nuclear β‐catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear β‐catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal β‐catenin staining (p<0.05). Forty‐five of the tumours, including two malignant lesions, were screened for β‐catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different β‐catenin staining patterns. There was an association between strong nuclear β‐catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours. Copyright © 2002 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>11920740</pmid><doi>10.1002/path.1067</doi><tpages>8</tpages></addata></record> |
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| subjects | APC beta Catenin Biological and medical sciences Breast Neoplasms - metabolism Breast Neoplasms - pathology cyclin D1 Cyclin D1 - metabolism Cytoskeletal Proteins - metabolism Disease Progression epithelial-stromal interactions Epithelium - pathology Female Gynecology. Andrology. Obstetrics Humans Immunoenzyme Techniques Loss of Heterozygosity Mammary gland diseases Medical sciences Neoplasm Proteins - metabolism phyllodes Phyllodes Tumor - metabolism Phyllodes Tumor - pathology Proto-Oncogene Proteins - metabolism RNA, Messenger - genetics RNA, Neoplasm - genetics Stromal Cells - pathology Trans-Activators Tumors Wnt Wnt Proteins Wnt2 Protein Zebrafish Proteins β-catenin |
| title | The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours |
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