Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas
Objective To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological d...
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| Veröffentlicht in: | Head & neck pathology (Totowa, N.J.) N.J.), 2024-11, Vol.18 (1), p.125, Article 125 |
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| creator | Coelho, Lívia Moreira Caetano Dantas, Thinali Sousa de Barros Silva, Paulo Goberlânio Barbosa, Jennifer Vianna Teixeira, André Costa Alves, Ana Paula Negreiros Nunes Mota, Mário Rogério Lima Vila, Pilar Gándara Ortega, Karem L. Sousa, Fabrício Bitu |
| description | Objective
To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher’s exact, Log-Rank Mantel Cox and Cox regression were performed. Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (
p
= 0.035) and mean MSH6 expression was significantly higher than MSH2 (
p
= 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (
p
= 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors. |
| doi_str_mv | 10.1007/s12105-024-01736-0 |
| format | Article |
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To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher’s exact, Log-Rank Mantel Cox and Cox regression were performed. Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (
p
= 0.035) and mean MSH6 expression was significantly higher than MSH2 (
p
= 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (
p
= 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.</description><identifier>ISSN: 1936-0568</identifier><identifier>EISSN: 1936-0568</identifier><identifier>DOI: 10.1007/s12105-024-01736-0</identifier><identifier>PMID: 39601931</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - metabolism ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Dentistry ; Disease-Free Survival ; DNA Mismatch Repair ; Female ; Humans ; Immunohistochemistry ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; MutS Homolog 2 Protein - analysis ; MutS Homolog 2 Protein - metabolism ; Oral and Maxillofacial Surgery ; Oropharyngeal Neoplasms - metabolism ; Oropharyngeal Neoplasms - mortality ; Oropharyngeal Neoplasms - pathology ; Otorhinolaryngology ; Pathology ; Squamous Cell Carcinoma of Head and Neck - metabolism ; Squamous Cell Carcinoma of Head and Neck - mortality ; Squamous Cell Carcinoma of Head and Neck - pathology</subject><ispartof>Head & neck pathology (Totowa, N.J.), 2024-11, Vol.18 (1), p.125, Article 125</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c228t-13abeb71b5e056f501901bdabfc5838f6e2f273767341845d5ef67cf8251686a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12105-024-01736-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12105-024-01736-0$$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/39601931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coelho, Lívia Moreira Caetano</creatorcontrib><creatorcontrib>Dantas, Thinali Sousa</creatorcontrib><creatorcontrib>de Barros Silva, Paulo Goberlânio</creatorcontrib><creatorcontrib>Barbosa, Jennifer Vianna</creatorcontrib><creatorcontrib>Teixeira, André Costa</creatorcontrib><creatorcontrib>Alves, Ana Paula Negreiros Nunes</creatorcontrib><creatorcontrib>Mota, Mário Rogério Lima</creatorcontrib><creatorcontrib>Vila, Pilar Gándara</creatorcontrib><creatorcontrib>Ortega, Karem L.</creatorcontrib><creatorcontrib>Sousa, Fabrício Bitu</creatorcontrib><title>Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas</title><title>Head & neck pathology (Totowa, N.J.)</title><addtitle>Head and Neck Pathol</addtitle><addtitle>Head Neck Pathol</addtitle><description>Objective
To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher’s exact, Log-Rank Mantel Cox and Cox regression were performed. Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (
p
= 0.035) and mean MSH6 expression was significantly higher than MSH2 (
p
= 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (
p
= 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Dentistry</subject><subject>Disease-Free Survival</subject><subject>DNA Mismatch Repair</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>MutS Homolog 2 Protein - analysis</subject><subject>MutS Homolog 2 Protein - metabolism</subject><subject>Oral and Maxillofacial Surgery</subject><subject>Oropharyngeal Neoplasms - metabolism</subject><subject>Oropharyngeal Neoplasms - mortality</subject><subject>Oropharyngeal Neoplasms - pathology</subject><subject>Otorhinolaryngology</subject><subject>Pathology</subject><subject>Squamous Cell Carcinoma of Head and Neck - metabolism</subject><subject>Squamous Cell Carcinoma of Head and Neck - mortality</subject><subject>Squamous Cell Carcinoma of Head and Neck - pathology</subject><issn>1936-0568</issn><issn>1936-0568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuFSEUhonR2Fp9AReGpZtRGAaYLs3Y6k2qNbauCcM9tDQDTDkzTfssvqxcbzWuXHHgfOfP-fkJec3ZO86Yfo-85Uw2rO0axrVQDXtCDvnxrpCqf_pPfUBeIN4wppju2HNyII4Vq01-SH5ukp9WSA5o9nQT45oy3M8FEENOu7cvAaNd3DX9DrMNhQ45zhPc028lLxAS0op9DAgWoTktAPRiLXfhzk40JPo1p6ber4Kz0_RALwvYBbb0vOT52paHdAWVu7hdbcwr0gGmiQ62uJBytPiSPPN2Qnj1eB6RH6cnl8Pn5uz802b4cNa4tu2Xhgs7wqj5KKF69bI6Y3zc2tE72YveK2h9q4VWWnS87-RWglfa-b6VXPXKiiPydq87l3y7Ai4mBnR1F5ugrmUEF6JTXGpV0XaPupIRC3gzlxCrE8OZ2YVi9qGYGor5HYphdejNo_46Rtj-HfmTQgXEHsDaqn9SzE1eS6qe_yf7C4QwmjI</recordid><startdate>20241127</startdate><enddate>20241127</enddate><creator>Coelho, Lívia Moreira Caetano</creator><creator>Dantas, Thinali Sousa</creator><creator>de Barros Silva, Paulo Goberlânio</creator><creator>Barbosa, Jennifer Vianna</creator><creator>Teixeira, André Costa</creator><creator>Alves, Ana Paula Negreiros Nunes</creator><creator>Mota, Mário Rogério Lima</creator><creator>Vila, Pilar Gándara</creator><creator>Ortega, Karem L.</creator><creator>Sousa, Fabrício Bitu</creator><general>Springer US</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>7X8</scope></search><sort><creationdate>20241127</creationdate><title>Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas</title><author>Coelho, Lívia Moreira Caetano ; Dantas, Thinali Sousa ; de Barros Silva, Paulo Goberlânio ; Barbosa, Jennifer Vianna ; Teixeira, André Costa ; Alves, Ana Paula Negreiros Nunes ; Mota, Mário Rogério Lima ; Vila, Pilar Gándara ; Ortega, Karem L. ; Sousa, Fabrício Bitu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c228t-13abeb71b5e056f501901bdabfc5838f6e2f273767341845d5ef67cf8251686a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Dentistry</topic><topic>Disease-Free Survival</topic><topic>DNA Mismatch Repair</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>MutS Homolog 2 Protein - analysis</topic><topic>MutS Homolog 2 Protein - metabolism</topic><topic>Oral and Maxillofacial Surgery</topic><topic>Oropharyngeal Neoplasms - metabolism</topic><topic>Oropharyngeal Neoplasms - mortality</topic><topic>Oropharyngeal Neoplasms - pathology</topic><topic>Otorhinolaryngology</topic><topic>Pathology</topic><topic>Squamous Cell Carcinoma of Head and Neck - metabolism</topic><topic>Squamous Cell Carcinoma of Head and Neck - mortality</topic><topic>Squamous Cell Carcinoma of Head and Neck - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coelho, Lívia Moreira Caetano</creatorcontrib><creatorcontrib>Dantas, Thinali Sousa</creatorcontrib><creatorcontrib>de Barros Silva, Paulo Goberlânio</creatorcontrib><creatorcontrib>Barbosa, Jennifer Vianna</creatorcontrib><creatorcontrib>Teixeira, André Costa</creatorcontrib><creatorcontrib>Alves, Ana Paula Negreiros Nunes</creatorcontrib><creatorcontrib>Mota, Mário Rogério Lima</creatorcontrib><creatorcontrib>Vila, Pilar Gándara</creatorcontrib><creatorcontrib>Ortega, Karem L.</creatorcontrib><creatorcontrib>Sousa, Fabrício Bitu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Head & neck pathology (Totowa, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coelho, Lívia Moreira Caetano</au><au>Dantas, Thinali Sousa</au><au>de Barros Silva, Paulo Goberlânio</au><au>Barbosa, Jennifer Vianna</au><au>Teixeira, André Costa</au><au>Alves, Ana Paula Negreiros Nunes</au><au>Mota, Mário Rogério Lima</au><au>Vila, Pilar Gándara</au><au>Ortega, Karem L.</au><au>Sousa, Fabrício Bitu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas</atitle><jtitle>Head & neck pathology (Totowa, N.J.)</jtitle><stitle>Head and Neck Pathol</stitle><addtitle>Head Neck Pathol</addtitle><date>2024-11-27</date><risdate>2024</risdate><volume>18</volume><issue>1</issue><spage>125</spage><pages>125-</pages><artnum>125</artnum><issn>1936-0568</issn><eissn>1936-0568</eissn><abstract>Objective
To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher’s exact, Log-Rank Mantel Cox and Cox regression were performed. Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (
p
= 0.035) and mean MSH6 expression was significantly higher than MSH2 (
p
= 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (
p
= 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39601931</pmid><doi>10.1007/s12105-024-01736-0</doi></addata></record> |
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| ispartof | Head & neck pathology (Totowa, N.J.), 2024-11, Vol.18 (1), p.125, Article 125 |
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| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor - analysis Biomarkers, Tumor - metabolism Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Dentistry Disease-Free Survival DNA Mismatch Repair Female Humans Immunohistochemistry Male Medicine Medicine & Public Health Middle Aged MutS Homolog 2 Protein - analysis MutS Homolog 2 Protein - metabolism Oral and Maxillofacial Surgery Oropharyngeal Neoplasms - metabolism Oropharyngeal Neoplasms - mortality Oropharyngeal Neoplasms - pathology Otorhinolaryngology Pathology Squamous Cell Carcinoma of Head and Neck - metabolism Squamous Cell Carcinoma of Head and Neck - mortality Squamous Cell Carcinoma of Head and Neck - pathology |
| title | Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas |
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