CR07*IMMUNOHISTOCHEMISTRY FOR LOSS OF EXPRESSION OF MISMATCH REPAIR GENE PROTEINS IN YOUNG PATIENTS WITH COLORECTAL CANCER: THE AUCKLAND EXPERIENCE
Identifieur interne : 001174 ( Istex/Corpus ); précédent : 001173; suivant : 001175CR07*IMMUNOHISTOCHEMISTRY FOR LOSS OF EXPRESSION OF MISMATCH REPAIR GENE PROTEINS IN YOUNG PATIENTS WITH COLORECTAL CANCER: THE AUCKLAND EXPERIENCE
Auteurs : D. M. Wright ; S. Parry ; J. Arnold ; I. Bissett ; M. Hulme Oir ; B. ParrySource :
- ANZ Journal of Surgery [ 1445-1433 ] ; 2009-05.
Abstract
Recently, in Australasia, a plea to screen all young patients with colorectal cancer (CRC) for Lynch syndrome has been advanced1. Since 2001 the three public hospitals in Auckland have had the policy of undertaking immunohistochemical (IHC) testing on the tumours of patients aged 50 years and under to detect loss of expression (LOE) of protein products for the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Purpose: To determine (1) the completeness of patient capture, (2) the incidence of LOE by IHC of the 4 gene proteins, and (3) to correlate IHC results with those of subsequent genetic testing for the corresponding germline mutations. Methodology: Retrospective review of the prospectively gathered clinical, pathological, and genetic records of all patients diagnosed with CRC aged 50 years and below between January 2001 and December 2007. Results: 244 patients aged 50 years or below with CRC were diagnosed in this period. 212 (86.9%) patients’ tumours underwent IHC, 147 of which had all 4 gene products studied. 30 (14.2%) tumours had LOE for one or more MMR proteins. 25/30 patients were offered genetic testing of whom 3 declined. So far 8 out of 16 patients tested have a confirmed germline mutation. Only 3/8 patients report a family history of CRC. Conclusion: Tumour IHC reveals LOE for one of the four MMR gene proteins in approximately 14% of young patients developing CRC and in half subsequent genetic testing will identify Lynch syndrome. A policy of mandatory testing is confirmed but audit of performance and appropriate referral is required.
Url:
DOI: 10.1111/j.1445-2197.2009.04915_7.x
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<front><div type="abstract" xml:lang="en">Recently, in Australasia, a plea to screen all young patients with colorectal cancer (CRC) for Lynch syndrome has been advanced1. Since 2001 the three public hospitals in Auckland have had the policy of undertaking immunohistochemical (IHC) testing on the tumours of patients aged 50 years and under to detect loss of expression (LOE) of protein products for the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Purpose: To determine (1) the completeness of patient capture, (2) the incidence of LOE by IHC of the 4 gene proteins, and (3) to correlate IHC results with those of subsequent genetic testing for the corresponding germline mutations. Methodology: Retrospective review of the prospectively gathered clinical, pathological, and genetic records of all patients diagnosed with CRC aged 50 years and below between January 2001 and December 2007. Results: 244 patients aged 50 years or below with CRC were diagnosed in this period. 212 (86.9%) patients’ tumours underwent IHC, 147 of which had all 4 gene products studied. 30 (14.2%) tumours had LOE for one or more MMR proteins. 25/30 patients were offered genetic testing of whom 3 declined. So far 8 out of 16 patients tested have a confirmed germline mutation. Only 3/8 patients report a family history of CRC. Conclusion: Tumour IHC reveals LOE for one of the four MMR gene proteins in approximately 14% of young patients developing CRC and in half subsequent genetic testing will identify Lynch syndrome. A policy of mandatory testing is confirmed but audit of performance and appropriate referral is required.</div>
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<abstractGroup><abstract type="main" xml:lang="en"><p>Recently, in Australasia, a plea to screen all young patients with colorectal cancer (CRC) for Lynch syndrome has been advanced<link href="#b1"><sup>1</sup>
</link>
.</p>
<p>Since 2001 the three public hospitals in Auckland have had the policy of undertaking immunohistochemical (IHC) testing on the tumours of patients aged 50 years and under to detect loss of expression (LOE) of protein products for the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2.</p>
<p><b>Purpose: </b>
To determine (1) the completeness of patient capture, (2) the incidence of LOE by IHC of the 4 gene proteins, and (3) to correlate IHC results with those of subsequent genetic testing for the corresponding germline mutations.</p>
<p><b>Methodology: </b>
Retrospective review of the prospectively gathered clinical, pathological, and genetic records of all patients diagnosed with CRC aged 50 years and below between January 2001 and December 2007.</p>
<p><b>Results: </b>
244 patients aged 50 years or below with CRC were diagnosed in this period. 212 (86.9%) patients’ tumours underwent IHC, 147 of which had all 4 gene products studied. 30 (14.2%) tumours had LOE for one or more MMR proteins. 25/30 patients were offered genetic testing of whom 3 declined. So far 8 out of 16 patients tested have a confirmed germline mutation. Only 3/8 patients report a family history of CRC.</p>
<p><b>Conclusion: </b>
Tumour IHC reveals LOE for one of the four MMR gene proteins in approximately 14% of young patients developing CRC and in half subsequent genetic testing will identify Lynch syndrome. A policy of mandatory testing is confirmed but audit of performance and appropriate referral is required.</p>
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<name type="personal"><namePart type="given">D. M.</namePart>
<namePart type="family">Wright</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">S.</namePart>
<namePart type="family">Parry</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">J.</namePart>
<namePart type="family">Arnold</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">I.</namePart>
<namePart type="family">Bissett</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">M.</namePart>
<namePart type="family">Hulme‐Moir</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">B.</namePart>
<namePart type="family">Parry</namePart>
<affiliation>Auckland City Hospital, Auckland, New Zealand</affiliation>
<role><roleTerm type="text">author</roleTerm>
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<originInfo><publisher>Blackwell Publishing Asia</publisher>
<place><placeTerm type="text">Melbourne, Australia</placeTerm>
</place>
<dateIssued encoding="w3cdtf">2009-05</dateIssued>
<copyrightDate encoding="w3cdtf">2009</copyrightDate>
</originInfo>
<language><languageTerm type="code" authority="rfc3066">en</languageTerm>
<languageTerm type="code" authority="iso639-2b">eng</languageTerm>
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<extent unit="words">5149</extent>
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<abstract lang="en">Recently, in Australasia, a plea to screen all young patients with colorectal cancer (CRC) for Lynch syndrome has been advanced1. Since 2001 the three public hospitals in Auckland have had the policy of undertaking immunohistochemical (IHC) testing on the tumours of patients aged 50 years and under to detect loss of expression (LOE) of protein products for the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Purpose: To determine (1) the completeness of patient capture, (2) the incidence of LOE by IHC of the 4 gene proteins, and (3) to correlate IHC results with those of subsequent genetic testing for the corresponding germline mutations. Methodology: Retrospective review of the prospectively gathered clinical, pathological, and genetic records of all patients diagnosed with CRC aged 50 years and below between January 2001 and December 2007. Results: 244 patients aged 50 years or below with CRC were diagnosed in this period. 212 (86.9%) patients’ tumours underwent IHC, 147 of which had all 4 gene products studied. 30 (14.2%) tumours had LOE for one or more MMR proteins. 25/30 patients were offered genetic testing of whom 3 declined. So far 8 out of 16 patients tested have a confirmed germline mutation. Only 3/8 patients report a family history of CRC. Conclusion: Tumour IHC reveals LOE for one of the four MMR gene proteins in approximately 14% of young patients developing CRC and in half subsequent genetic testing will identify Lynch syndrome. A policy of mandatory testing is confirmed but audit of performance and appropriate referral is required.</abstract>
<relatedItem type="host"><titleInfo><title>ANZ Journal of Surgery</title>
</titleInfo>
<genre type="journal">journal</genre>
<identifier type="ISSN">1445-1433</identifier>
<identifier type="eISSN">1445-2197</identifier>
<identifier type="DOI">10.1111/(ISSN)1445-2197</identifier>
<identifier type="PublisherID">ANS</identifier>
<part><date>2009</date>
<detail type="title"><title>Abstracts of the Royal Australasian College of Surgeons Annual Scientific Congress, 6–9 May 2009, Brisbane, Queensland, Australia</title>
</detail>
<detail type="volume"><caption>vol.</caption>
<number>79</number>
</detail>
<detail type="supplement"><caption>Suppl. no.</caption>
<number>s1</number>
</detail>
<extent unit="pages"><start>A10</start>
<end>A10</end>
<total>1</total>
</extent>
</part>
</relatedItem>
<identifier type="istex">C61AF7AD23BF14689F1B4649130DCC991B2F94A3</identifier>
<identifier type="DOI">10.1111/j.1445-2197.2009.04915_7.x</identifier>
<identifier type="ArticleID">ANS4915_7</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Journal compilation © 2009 The Royal Australasian College of Surgeons</accessCondition>
<recordInfo><recordContentSource>WILEY</recordContentSource>
<recordOrigin>Blackwell Publishing Asia</recordOrigin>
</recordInfo>
</mods>
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<serie></serie>
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