How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?
Summary Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens aft...
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| creator | Vilkin, Alex, MD Halpern, Marisa, MD Morgenstern, Sara, MD Brazovski, Eli, MD Gingold-Belfer, Rachel, MD Boltin, Doron, MD Purim, Ofer, MD Kundel, Yulia, MD Welinsky, Sara, MD Brenner, Baruch, MD Niv, Yaron, MD Levi, Zohar, MD |
| description | Summary Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control ( P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group ( P = .009). In the neoadjuvant group, a disagreement pattern of “endoscopic strong operative focal” was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining. |
| doi_str_mv | 10.1016/j.humpath.2014.07.005 |
| format | Article |
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We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control ( P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group ( P = .009). In the neoadjuvant group, a disagreement pattern of “endoscopic strong operative focal” was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2014.07.005</identifier><identifier>PMID: 25150747</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing - analysis ; Adaptor Proteins, Signal Transducing - drug effects ; Adaptor Proteins, Signal Transducing - radiation effects ; Adenosine Triphosphatases - analysis ; Adenosine Triphosphatases - drug effects ; Adenosine Triphosphatases - radiation effects ; Aged ; Cancer therapies ; Chemoradiation ; Chemoradiotherapy ; Cloning ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - therapy ; Deoxyribonucleic acid ; DNA ; DNA Mismatch Repair ; DNA Repair Enzymes - analysis ; DNA Repair Enzymes - drug effects ; DNA Repair Enzymes - radiation effects ; DNA-Binding Proteins - analysis ; DNA-Binding Proteins - drug effects ; DNA-Binding Proteins - radiation effects ; Female ; HNPCC ; Humans ; Immunohistochemical staining ; Immunohistochemistry - standards ; Lynch ; Male ; Middle Aged ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein - analysis ; MutS Homolog 2 Protein - drug effects ; MutS Homolog 2 Protein - radiation effects ; Neoadjuvant ; Neoadjuvant Therapy ; Neoplasm Proteins - analysis ; Neoplasm Proteins - drug effects ; Neoplasm Proteins - radiation effects ; Nuclear Proteins - analysis ; Nuclear Proteins - drug effects ; Nuclear Proteins - radiation effects ; Pathology ; Proteins ; Reliability ; Reproducibility of Results ; Surgery</subject><ispartof>Human pathology, 2014-10, Vol.45 (10), p.2029-2036</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-1b2d48e82e713f1ac91c1dde9f763084df7638b0f48a435aecb12e79c6b396763</citedby><cites>FETCH-LOGICAL-c514t-1b2d48e82e713f1ac91c1dde9f763084df7638b0f48a435aecb12e79c6b396763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817714002871$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25150747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vilkin, Alex, MD</creatorcontrib><creatorcontrib>Halpern, Marisa, MD</creatorcontrib><creatorcontrib>Morgenstern, Sara, MD</creatorcontrib><creatorcontrib>Brazovski, Eli, MD</creatorcontrib><creatorcontrib>Gingold-Belfer, Rachel, MD</creatorcontrib><creatorcontrib>Boltin, Doron, MD</creatorcontrib><creatorcontrib>Purim, Ofer, MD</creatorcontrib><creatorcontrib>Kundel, Yulia, MD</creatorcontrib><creatorcontrib>Welinsky, Sara, MD</creatorcontrib><creatorcontrib>Brenner, Baruch, MD</creatorcontrib><creatorcontrib>Niv, Yaron, MD</creatorcontrib><creatorcontrib>Levi, Zohar, MD</creatorcontrib><title>How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control ( P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group ( P = .009). In the neoadjuvant group, a disagreement pattern of “endoscopic strong operative focal” was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.</description><subject>Adaptor Proteins, Signal Transducing - analysis</subject><subject>Adaptor Proteins, Signal Transducing - drug effects</subject><subject>Adaptor Proteins, Signal Transducing - radiation effects</subject><subject>Adenosine Triphosphatases - analysis</subject><subject>Adenosine Triphosphatases - drug effects</subject><subject>Adenosine Triphosphatases - radiation effects</subject><subject>Aged</subject><subject>Cancer therapies</subject><subject>Chemoradiation</subject><subject>Chemoradiotherapy</subject><subject>Cloning</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Mismatch Repair</subject><subject>DNA Repair Enzymes - analysis</subject><subject>DNA Repair Enzymes - drug effects</subject><subject>DNA Repair Enzymes - radiation effects</subject><subject>DNA-Binding Proteins - analysis</subject><subject>DNA-Binding Proteins - drug effects</subject><subject>DNA-Binding Proteins - radiation effects</subject><subject>Female</subject><subject>HNPCC</subject><subject>Humans</subject><subject>Immunohistochemical staining</subject><subject>Immunohistochemistry - standards</subject><subject>Lynch</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mismatch Repair Endonuclease PMS2</subject><subject>MutL Protein Homolog 1</subject><subject>MutS Homolog 2 Protein - analysis</subject><subject>MutS Homolog 2 Protein - drug effects</subject><subject>MutS Homolog 2 Protein - radiation effects</subject><subject>Neoadjuvant</subject><subject>Neoadjuvant Therapy</subject><subject>Neoplasm Proteins - analysis</subject><subject>Neoplasm Proteins - drug effects</subject><subject>Neoplasm Proteins - radiation effects</subject><subject>Nuclear Proteins - analysis</subject><subject>Nuclear Proteins - drug effects</subject><subject>Nuclear Proteins - radiation effects</subject><subject>Pathology</subject><subject>Proteins</subject><subject>Reliability</subject><subject>Reproducibility of Results</subject><subject>Surgery</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkuP1DAMgCsEYoeFnwCKxGUvLXaavi6sVstjkVZwAM5Rmro0pW2GJF00_55UM4C0Fzj5kM-O7c9J8hwhQ8Dy1ZgN67xXYcg4oMigygCKB8kOi5yndd7wh8kOQJRpjVV1ljzxfgRALETxODnjBRZQiWqXHG7sT-ZoMqqdiBnPzDyvix2MD1YPNButJuaDMotZvrHeOvbm4xWbjZ9V0EPM3Cvj2N7ZQGbxbE8uMjN1TPWBHFvIqm5c79QS2FbOOtUZFYxdLp8mj3o1eXp2iufJ13dvv1zfpLef3n-4vrpNdYEipNjyTtRUc6ow71HpBjV2HTV9VeZQi26LdQu9qJXIC0W6xcg2umzzpoxv58nFsW5s8sdKPsjYvaZpUrG51Uss8wLyuA34DxSxhAZ4HdGX99DRrm6Jg2yUEJxXsFHFkdLOeu-ol3tnZuUOEkFuGuUoTxrlplFCJaPGmPfiVH1t4zL_ZP32FoHLI0Bxc3eGnPTa0KKpM450kJ01__zi9b0KeoqSo-7vdCD_dxrpuQT5ebul7ZRQQJw_uvgFqBrG6w</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Vilkin, Alex, MD</creator><creator>Halpern, Marisa, MD</creator><creator>Morgenstern, Sara, MD</creator><creator>Brazovski, Eli, MD</creator><creator>Gingold-Belfer, Rachel, MD</creator><creator>Boltin, Doron, MD</creator><creator>Purim, Ofer, MD</creator><creator>Kundel, Yulia, MD</creator><creator>Welinsky, Sara, MD</creator><creator>Brenner, Baruch, MD</creator><creator>Niv, Yaron, MD</creator><creator>Levi, Zohar, MD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>K9.</scope><scope>7X8</scope><scope>7TM</scope></search><sort><creationdate>20141001</creationdate><title>How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?</title><author>Vilkin, Alex, MD ; Halpern, Marisa, MD ; Morgenstern, Sara, MD ; Brazovski, Eli, MD ; Gingold-Belfer, Rachel, MD ; Boltin, Doron, MD ; Purim, Ofer, MD ; Kundel, Yulia, MD ; Welinsky, Sara, MD ; Brenner, Baruch, MD ; Niv, Yaron, MD ; Levi, Zohar, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-1b2d48e82e713f1ac91c1dde9f763084df7638b0f48a435aecb12e79c6b396763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Signal Transducing - analysis</topic><topic>Adaptor Proteins, Signal Transducing - drug effects</topic><topic>Adaptor Proteins, Signal Transducing - radiation effects</topic><topic>Adenosine Triphosphatases - analysis</topic><topic>Adenosine Triphosphatases - drug effects</topic><topic>Adenosine Triphosphatases - radiation effects</topic><topic>Aged</topic><topic>Cancer therapies</topic><topic>Chemoradiation</topic><topic>Chemoradiotherapy</topic><topic>Cloning</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - therapy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Mismatch Repair</topic><topic>DNA Repair Enzymes - analysis</topic><topic>DNA Repair Enzymes - drug effects</topic><topic>DNA Repair Enzymes - radiation effects</topic><topic>DNA-Binding Proteins - analysis</topic><topic>DNA-Binding Proteins - drug effects</topic><topic>DNA-Binding Proteins - radiation effects</topic><topic>Female</topic><topic>HNPCC</topic><topic>Humans</topic><topic>Immunohistochemical staining</topic><topic>Immunohistochemistry - standards</topic><topic>Lynch</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mismatch Repair Endonuclease PMS2</topic><topic>MutL Protein Homolog 1</topic><topic>MutS Homolog 2 Protein - analysis</topic><topic>MutS Homolog 2 Protein - drug effects</topic><topic>MutS Homolog 2 Protein - radiation effects</topic><topic>Neoadjuvant</topic><topic>Neoadjuvant Therapy</topic><topic>Neoplasm Proteins - analysis</topic><topic>Neoplasm Proteins - drug effects</topic><topic>Neoplasm Proteins - radiation effects</topic><topic>Nuclear Proteins - analysis</topic><topic>Nuclear Proteins - drug effects</topic><topic>Nuclear Proteins - radiation effects</topic><topic>Pathology</topic><topic>Proteins</topic><topic>Reliability</topic><topic>Reproducibility of Results</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vilkin, Alex, MD</creatorcontrib><creatorcontrib>Halpern, Marisa, MD</creatorcontrib><creatorcontrib>Morgenstern, Sara, MD</creatorcontrib><creatorcontrib>Brazovski, Eli, MD</creatorcontrib><creatorcontrib>Gingold-Belfer, Rachel, MD</creatorcontrib><creatorcontrib>Boltin, Doron, MD</creatorcontrib><creatorcontrib>Purim, Ofer, MD</creatorcontrib><creatorcontrib>Kundel, Yulia, MD</creatorcontrib><creatorcontrib>Welinsky, Sara, MD</creatorcontrib><creatorcontrib>Brenner, Baruch, MD</creatorcontrib><creatorcontrib>Niv, Yaron, MD</creatorcontrib><creatorcontrib>Levi, Zohar, MD</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 Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vilkin, Alex, MD</au><au>Halpern, Marisa, MD</au><au>Morgenstern, Sara, MD</au><au>Brazovski, Eli, MD</au><au>Gingold-Belfer, Rachel, MD</au><au>Boltin, Doron, MD</au><au>Purim, Ofer, MD</au><au>Kundel, Yulia, MD</au><au>Welinsky, Sara, MD</au><au>Brenner, Baruch, MD</au><au>Niv, Yaron, MD</au><au>Levi, Zohar, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>45</volume><issue>10</issue><spage>2029</spage><epage>2036</epage><pages>2029-2036</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control ( P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group ( P = .009). In the neoadjuvant group, a disagreement pattern of “endoscopic strong operative focal” was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25150747</pmid><doi>10.1016/j.humpath.2014.07.005</doi><tpages>8</tpages></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - analysis Adaptor Proteins, Signal Transducing - drug effects Adaptor Proteins, Signal Transducing - radiation effects Adenosine Triphosphatases - analysis Adenosine Triphosphatases - drug effects Adenosine Triphosphatases - radiation effects Aged Cancer therapies Chemoradiation Chemoradiotherapy Cloning Colorectal Neoplasms - genetics Colorectal Neoplasms - therapy Deoxyribonucleic acid DNA DNA Mismatch Repair DNA Repair Enzymes - analysis DNA Repair Enzymes - drug effects DNA Repair Enzymes - radiation effects DNA-Binding Proteins - analysis DNA-Binding Proteins - drug effects DNA-Binding Proteins - radiation effects Female HNPCC Humans Immunohistochemical staining Immunohistochemistry - standards Lynch Male Middle Aged Mismatch Repair Endonuclease PMS2 MutL Protein Homolog 1 MutS Homolog 2 Protein - analysis MutS Homolog 2 Protein - drug effects MutS Homolog 2 Protein - radiation effects Neoadjuvant Neoadjuvant Therapy Neoplasm Proteins - analysis Neoplasm Proteins - drug effects Neoplasm Proteins - radiation effects Nuclear Proteins - analysis Nuclear Proteins - drug effects Nuclear Proteins - radiation effects Pathology Proteins Reliability Reproducibility of Results Surgery |
| title | How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation? |
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