Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?
Purpose The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer. Methods A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities incl...
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| Veröffentlicht in: | Annals of surgical oncology 2012-03, Vol.19 (3), p.809-816 |
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| creator | Canard, Guillaume Lefevre, Jeremie H. Colas, Chrystelle Coulet, Florence Svrcek, Magali Lascols, Olivier Hamelin, Richard Shields, Conor Duval, Alex Fléjou, Jean-Francois Soubrier, Florent Tiret, Emmanuel Parc, Yann |
| description | Purpose
The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.
Methods
A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.
Results
A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (
n
= 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of
MSH2
on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.
Conclusions
Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients. |
| doi_str_mv | 10.1245/s10434-011-2014-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_922762506</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>922762506</sourcerecordid><originalsourceid>FETCH-LOGICAL-c436t-2b4649cf7ecadfb5b8cf98deb943379c6bb17df24f93b6005218397cb669c4383</originalsourceid><addsrcrecordid>eNp1kEtLAzEYRYMotlZ_gBsJblyN5jXJxI2UsVah4KKKyzDJZPpgmtSks-i_N6VVQXCVkJx7vo8LwCVGt5iw_C5ixCjLEMYZQZhl4gj0cZ5eGC_wcbojXmSS8LwHzmJcIoQFRfkp6BFcCElE3gfjqQnWuoWbwcYHONk6M4fTrauDX1m4cLD0rQ_WbKoWlpUzNtzDYbDww8JHv0uNnO9m84dzcNJUbbQXh3MA3p9Gb-VzNnkdv5TDSWYY5ZuMaMaZNI2wpqobnevCNLKorZaMUiEN1xqLuiGskVRzhPK0KZXCaM5lMhR0AG723nXwn52NG7VaRGPbtnLWd1FJQgQnOeKJvP5DLn0XXFouQZiSAsmdDu8hE3yMwTZqHRarKmwVRmrXsdp3rFLHatexEilzdRB3emXrn8R3qQkgeyCmLzez4Xfy_9YvdvOErA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>921328098</pqid></control><display><type>article</type><title>Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Canard, Guillaume ; Lefevre, Jeremie H. ; Colas, Chrystelle ; Coulet, Florence ; Svrcek, Magali ; Lascols, Olivier ; Hamelin, Richard ; Shields, Conor ; Duval, Alex ; Fléjou, Jean-Francois ; Soubrier, Florent ; Tiret, Emmanuel ; Parc, Yann</creator><creatorcontrib>Canard, Guillaume ; Lefevre, Jeremie H. ; Colas, Chrystelle ; Coulet, Florence ; Svrcek, Magali ; Lascols, Olivier ; Hamelin, Richard ; Shields, Conor ; Duval, Alex ; Fléjou, Jean-Francois ; Soubrier, Florent ; Tiret, Emmanuel ; Parc, Yann</creatorcontrib><description>Purpose
The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.
Methods
A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.
Results
A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (
n
= 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of
MSH2
on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.
Conclusions
Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-011-2014-7</identifier><identifier>PMID: 21879275</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Adaptor Proteins, Signal Transducing - analysis ; Adult ; Aged ; Aged, 80 and over ; Colorectal Cancer ; Colorectal Neoplasms - surgery ; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis ; DNA Methylation ; DNA-Binding Proteins ; Female ; Genetic Testing ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Male ; Medicine ; Medicine & Public Health ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein - analysis ; Nuclear Proteins - analysis ; Oncology ; Promoter Regions, Genetic ; Surgery ; Surgical Oncology ; Young Adult</subject><ispartof>Annals of surgical oncology, 2012-03, Vol.19 (3), p.809-816</ispartof><rights>Society of Surgical Oncology 2011</rights><rights>Society of Surgical Oncology 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-2b4649cf7ecadfb5b8cf98deb943379c6bb17df24f93b6005218397cb669c4383</citedby><cites>FETCH-LOGICAL-c436t-2b4649cf7ecadfb5b8cf98deb943379c6bb17df24f93b6005218397cb669c4383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-011-2014-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-011-2014-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21879275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Canard, Guillaume</creatorcontrib><creatorcontrib>Lefevre, Jeremie H.</creatorcontrib><creatorcontrib>Colas, Chrystelle</creatorcontrib><creatorcontrib>Coulet, Florence</creatorcontrib><creatorcontrib>Svrcek, Magali</creatorcontrib><creatorcontrib>Lascols, Olivier</creatorcontrib><creatorcontrib>Hamelin, Richard</creatorcontrib><creatorcontrib>Shields, Conor</creatorcontrib><creatorcontrib>Duval, Alex</creatorcontrib><creatorcontrib>Fléjou, Jean-Francois</creatorcontrib><creatorcontrib>Soubrier, Florent</creatorcontrib><creatorcontrib>Tiret, Emmanuel</creatorcontrib><creatorcontrib>Parc, Yann</creatorcontrib><title>Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Purpose
The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.
Methods
A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.
Results
A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (
n
= 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of
MSH2
on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.
Conclusions
Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.</description><subject>Adaptor Proteins, Signal Transducing - analysis</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Colorectal Cancer</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins</subject><subject>Female</subject><subject>Genetic Testing</subject><subject>Germ-Line Mutation</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microsatellite Instability</subject><subject>Middle Aged</subject><subject>MutL Protein Homolog 1</subject><subject>MutS Homolog 2 Protein - analysis</subject><subject>Nuclear Proteins - analysis</subject><subject>Oncology</subject><subject>Promoter Regions, Genetic</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Young Adult</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kEtLAzEYRYMotlZ_gBsJblyN5jXJxI2UsVah4KKKyzDJZPpgmtSks-i_N6VVQXCVkJx7vo8LwCVGt5iw_C5ixCjLEMYZQZhl4gj0cZ5eGC_wcbojXmSS8LwHzmJcIoQFRfkp6BFcCElE3gfjqQnWuoWbwcYHONk6M4fTrauDX1m4cLD0rQ_WbKoWlpUzNtzDYbDww8JHv0uNnO9m84dzcNJUbbQXh3MA3p9Gb-VzNnkdv5TDSWYY5ZuMaMaZNI2wpqobnevCNLKorZaMUiEN1xqLuiGskVRzhPK0KZXCaM5lMhR0AG723nXwn52NG7VaRGPbtnLWd1FJQgQnOeKJvP5DLn0XXFouQZiSAsmdDu8hE3yMwTZqHRarKmwVRmrXsdp3rFLHatexEilzdRB3emXrn8R3qQkgeyCmLzez4Xfy_9YvdvOErA</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Canard, Guillaume</creator><creator>Lefevre, Jeremie H.</creator><creator>Colas, Chrystelle</creator><creator>Coulet, Florence</creator><creator>Svrcek, Magali</creator><creator>Lascols, Olivier</creator><creator>Hamelin, Richard</creator><creator>Shields, Conor</creator><creator>Duval, Alex</creator><creator>Fléjou, Jean-Francois</creator><creator>Soubrier, Florent</creator><creator>Tiret, Emmanuel</creator><creator>Parc, Yann</creator><general>Springer-Verlag</general><general>Springer Nature B.V</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20120301</creationdate><title>Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?</title><author>Canard, Guillaume ; Lefevre, Jeremie H. ; Colas, Chrystelle ; Coulet, Florence ; Svrcek, Magali ; Lascols, Olivier ; Hamelin, Richard ; Shields, Conor ; Duval, Alex ; Fléjou, Jean-Francois ; Soubrier, Florent ; Tiret, Emmanuel ; Parc, Yann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-2b4649cf7ecadfb5b8cf98deb943379c6bb17df24f93b6005218397cb669c4383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adaptor Proteins, Signal Transducing - analysis</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Colorectal Cancer</topic><topic>Colorectal Neoplasms - surgery</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</topic><topic>DNA Methylation</topic><topic>DNA-Binding Proteins</topic><topic>Female</topic><topic>Genetic Testing</topic><topic>Germ-Line Mutation</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Microsatellite Instability</topic><topic>Middle Aged</topic><topic>MutL Protein Homolog 1</topic><topic>MutS Homolog 2 Protein - analysis</topic><topic>Nuclear Proteins - analysis</topic><topic>Oncology</topic><topic>Promoter Regions, Genetic</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Canard, Guillaume</creatorcontrib><creatorcontrib>Lefevre, Jeremie H.</creatorcontrib><creatorcontrib>Colas, Chrystelle</creatorcontrib><creatorcontrib>Coulet, Florence</creatorcontrib><creatorcontrib>Svrcek, Magali</creatorcontrib><creatorcontrib>Lascols, Olivier</creatorcontrib><creatorcontrib>Hamelin, Richard</creatorcontrib><creatorcontrib>Shields, Conor</creatorcontrib><creatorcontrib>Duval, Alex</creatorcontrib><creatorcontrib>Fléjou, Jean-Francois</creatorcontrib><creatorcontrib>Soubrier, Florent</creatorcontrib><creatorcontrib>Tiret, Emmanuel</creatorcontrib><creatorcontrib>Parc, Yann</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Canard, Guillaume</au><au>Lefevre, Jeremie H.</au><au>Colas, Chrystelle</au><au>Coulet, Florence</au><au>Svrcek, Magali</au><au>Lascols, Olivier</au><au>Hamelin, Richard</au><au>Shields, Conor</au><au>Duval, Alex</au><au>Fléjou, Jean-Francois</au><au>Soubrier, Florent</au><au>Tiret, Emmanuel</au><au>Parc, Yann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>19</volume><issue>3</issue><spage>809</spage><epage>816</epage><pages>809-816</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract>Purpose
The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.
Methods
A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.
Results
A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (
n
= 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of
MSH2
on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.
Conclusions
Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>21879275</pmid><doi>10.1245/s10434-011-2014-7</doi><tpages>8</tpages></addata></record> |
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| ispartof | Annals of surgical oncology, 2012-03, Vol.19 (3), p.809-816 |
| issn | 1068-9265 1534-4681 |
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| subjects | Adaptor Proteins, Signal Transducing - analysis Adult Aged Aged, 80 and over Colorectal Cancer Colorectal Neoplasms - surgery Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis DNA Methylation DNA-Binding Proteins Female Genetic Testing Germ-Line Mutation Humans Immunohistochemistry Male Medicine Medicine & Public Health Microsatellite Instability Middle Aged MutL Protein Homolog 1 MutS Homolog 2 Protein - analysis Nuclear Proteins - analysis Oncology Promoter Regions, Genetic Surgery Surgical Oncology Young Adult |
| title | Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough? |
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