The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma
There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with...
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creator | da Costa, Alexandre A. B. A. Costa, Felipe D’Almeida Araújo, Daniel Vilarim Camandaroba, Marcos Pedro Guedes de Jesus, Victor Hugo Fonseca Oliveira, Audrey Alves, Ana Caroline Fonseca Stecca, Carlos Machado, Larissa de Oliveira, Andrea Cruz Feraz de Oliveira, Thiago Bueno Nicolau, Ulisses Ribaldo de Lima, Vladmir Cláudio Cordeiro |
description | There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone (
n
= 37) or chemotherapy with cetuximab (
n
= 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, (
p
= 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (
p
= 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (
p
= 0.002) and a mPFS of 3.2 months versus 4.7 months (
p
= 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08;
p
= 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99;
p
= 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response. |
doi_str_mv | 10.1007/s12032-018-1234-0 |
format | Article |
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n
= 37) or chemotherapy with cetuximab (
n
= 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, (
p
= 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (
p
= 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (
p
= 0.002) and a mPFS of 3.2 months versus 4.7 months (
p
= 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08;
p
= 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99;
p
= 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.</description><identifier>ISSN: 1357-0560</identifier><identifier>ISSN: 1559-131X</identifier><identifier>EISSN: 1559-131X</identifier><identifier>DOI: 10.1007/s12032-018-1234-0</identifier><identifier>PMID: 30478503</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aged ; Antineoplastic Agents, Immunological - therapeutic use ; BIOLOGICAL MARKERS ; Biomarkers, Tumor - analysis ; CARCINOMAS ; Cetuximab - therapeutic use ; CHEMOTHERAPY ; COMPUTERIZED TOMOGRAPHY ; Cyclin-Dependent Kinase Inhibitor p18 - metabolism ; Drug Resistance, Neoplasm - physiology ; Female ; HEAD ; Head & neck cancer ; Hematology ; Humans ; Immunotherapy ; Internal Medicine ; Kaplan-Meier Estimate ; Male ; Medicine ; Medicine & Public Health ; METASTASES ; Middle Aged ; Monoclonal antibodies ; NECK ; Oncology ; Original Paper ; Pathology ; PATIENTS ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; PROTEINS ; Proto-Oncogene Proteins c-met - metabolism ; PTEN Phosphohydrolase - metabolism ; RADIOLOGY AND NUCLEAR MEDICINE ; Retrospective Studies ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - drug therapy ; Squamous Cell Carcinoma of Head and Neck - mortality ; Targeted cancer therapy</subject><ispartof>Medical oncology (Northwood, London, England), 2019-01, Vol.36 (1), p.8-9, Article 8</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Medical Oncology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-f7b3c34654b77fe9c5917281da4fd9fe8b2f2bf56c2ffb2e98ebb2d972294c773</citedby><cites>FETCH-LOGICAL-c400t-f7b3c34654b77fe9c5917281da4fd9fe8b2f2bf56c2ffb2e98ebb2d972294c773</cites><orcidid>0000-0002-1631-0105</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12032-018-1234-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12032-018-1234-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,315,782,786,887,27933,27934,41497,42566,51328</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30478503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22938453$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>da Costa, Alexandre A. B. A.</creatorcontrib><creatorcontrib>Costa, Felipe D’Almeida</creatorcontrib><creatorcontrib>Araújo, Daniel Vilarim</creatorcontrib><creatorcontrib>Camandaroba, Marcos Pedro Guedes</creatorcontrib><creatorcontrib>de Jesus, Victor Hugo Fonseca</creatorcontrib><creatorcontrib>Oliveira, Audrey</creatorcontrib><creatorcontrib>Alves, Ana Caroline Fonseca</creatorcontrib><creatorcontrib>Stecca, Carlos</creatorcontrib><creatorcontrib>Machado, Larissa</creatorcontrib><creatorcontrib>de Oliveira, Andrea Cruz Feraz</creatorcontrib><creatorcontrib>de Oliveira, Thiago Bueno</creatorcontrib><creatorcontrib>Nicolau, Ulisses Ribaldo</creatorcontrib><creatorcontrib>de Lima, Vladmir Cláudio Cordeiro</creatorcontrib><title>The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone (
n
= 37) or chemotherapy with cetuximab (
n
= 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, (
p
= 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (
p
= 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (
p
= 0.002) and a mPFS of 3.2 months versus 4.7 months (
p
= 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08;
p
= 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99;
p
= 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents, Immunological - therapeutic use</subject><subject>BIOLOGICAL MARKERS</subject><subject>Biomarkers, Tumor - analysis</subject><subject>CARCINOMAS</subject><subject>Cetuximab - therapeutic use</subject><subject>CHEMOTHERAPY</subject><subject>COMPUTERIZED TOMOGRAPHY</subject><subject>Cyclin-Dependent Kinase Inhibitor p18 - metabolism</subject><subject>Drug Resistance, Neoplasm - physiology</subject><subject>Female</subject><subject>HEAD</subject><subject>Head & neck cancer</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Internal Medicine</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>METASTASES</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>NECK</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>PATIENTS</subject><subject>Prognosis</subject><subject>Progression-Free Survival</subject><subject>Proportional Hazards Models</subject><subject>PROTEINS</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>Retrospective Studies</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - drug therapy</subject><subject>Squamous Cell Carcinoma of Head and Neck - mortality</subject><subject>Targeted cancer therapy</subject><issn>1357-0560</issn><issn>1559-131X</issn><issn>1559-131X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kUtv1TAQhS0Eog_4AWyQJTYsGvAzjpeourRILbC4SOws2xlzU27sWzuR6L-vQ0phw2oszTdnzvgg9IqSd5QQ9b5QRjhrCO0ayrhoyBN0TKXUDeX0-9P65lI1RLbkCJ2UckMIo5Lp5-iIE6E6Sfgx6rc7wDntoeAU8Nft5vMZ9teb7Rm2sccH2uIh4gxlKJONHvCUsIdp_jWM1i2tHdj-NxrB_8TldrZjmktl9nvsbfZDTKN9gZ4Fuy_w8qGeom8fN9vzy-bqy8Wn8w9XjReETE1QjnsuWimcUgG0l5oq1tHeitDrAJ1jgbkgW89CcAx0B86xXivGtPBK8VP0ZtVNZRpM8cMEfudTrN4mUyHeCckr9XalDjndzlAmMw5lMWwjVO-GUd61ohPdP4KP6E2ac6w3LJRSmomWVYqulM-plAzBHHL9n3xnKDFLUGYNytSgzBKUIXXm9YPy7EboHyf-JFMBtgKltuIPyH9X_1_1Hv0smwE</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>da Costa, Alexandre A. B. A.</creator><creator>Costa, Felipe D’Almeida</creator><creator>Araújo, Daniel Vilarim</creator><creator>Camandaroba, Marcos Pedro Guedes</creator><creator>de Jesus, Victor Hugo Fonseca</creator><creator>Oliveira, Audrey</creator><creator>Alves, Ana Caroline Fonseca</creator><creator>Stecca, Carlos</creator><creator>Machado, Larissa</creator><creator>de Oliveira, Andrea Cruz Feraz</creator><creator>de Oliveira, Thiago Bueno</creator><creator>Nicolau, Ulisses Ribaldo</creator><creator>de Lima, Vladmir Cláudio Cordeiro</creator><general>Springer US</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>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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0002-1631-0105</orcidid></search><sort><creationdate>20190101</creationdate><title>The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma</title><author>da Costa, Alexandre A. B. A. ; Costa, Felipe D’Almeida ; Araújo, Daniel Vilarim ; Camandaroba, Marcos Pedro Guedes ; de Jesus, Victor Hugo Fonseca ; Oliveira, Audrey ; Alves, Ana Caroline Fonseca ; Stecca, Carlos ; Machado, Larissa ; de Oliveira, Andrea Cruz Feraz ; de Oliveira, Thiago Bueno ; Nicolau, Ulisses Ribaldo ; de Lima, Vladmir Cláudio Cordeiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-f7b3c34654b77fe9c5917281da4fd9fe8b2f2bf56c2ffb2e98ebb2d972294c773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents, Immunological - therapeutic use</topic><topic>BIOLOGICAL MARKERS</topic><topic>Biomarkers, Tumor - analysis</topic><topic>CARCINOMAS</topic><topic>Cetuximab - therapeutic use</topic><topic>CHEMOTHERAPY</topic><topic>COMPUTERIZED TOMOGRAPHY</topic><topic>Cyclin-Dependent Kinase Inhibitor p18 - metabolism</topic><topic>Drug Resistance, Neoplasm - physiology</topic><topic>Female</topic><topic>HEAD</topic><topic>Head & neck cancer</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Internal Medicine</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>METASTASES</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>NECK</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>PATIENTS</topic><topic>Prognosis</topic><topic>Progression-Free Survival</topic><topic>Proportional Hazards Models</topic><topic>PROTEINS</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>Retrospective Studies</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - drug therapy</topic><topic>Squamous Cell Carcinoma of Head and Neck - mortality</topic><topic>Targeted cancer therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>da Costa, Alexandre A. B. A.</creatorcontrib><creatorcontrib>Costa, Felipe D’Almeida</creatorcontrib><creatorcontrib>Araújo, Daniel Vilarim</creatorcontrib><creatorcontrib>Camandaroba, Marcos Pedro Guedes</creatorcontrib><creatorcontrib>de Jesus, Victor Hugo Fonseca</creatorcontrib><creatorcontrib>Oliveira, Audrey</creatorcontrib><creatorcontrib>Alves, Ana Caroline Fonseca</creatorcontrib><creatorcontrib>Stecca, Carlos</creatorcontrib><creatorcontrib>Machado, Larissa</creatorcontrib><creatorcontrib>de Oliveira, Andrea Cruz Feraz</creatorcontrib><creatorcontrib>de Oliveira, Thiago Bueno</creatorcontrib><creatorcontrib>Nicolau, Ulisses Ribaldo</creatorcontrib><creatorcontrib>de Lima, Vladmir Cláudio Cordeiro</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>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>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><collection>OSTI.GOV</collection><jtitle>Medical oncology (Northwood, London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>da Costa, Alexandre A. B. A.</au><au>Costa, Felipe D’Almeida</au><au>Araújo, Daniel Vilarim</au><au>Camandaroba, Marcos Pedro Guedes</au><au>de Jesus, Victor Hugo Fonseca</au><au>Oliveira, Audrey</au><au>Alves, Ana Caroline Fonseca</au><au>Stecca, Carlos</au><au>Machado, Larissa</au><au>de Oliveira, Andrea Cruz Feraz</au><au>de Oliveira, Thiago Bueno</au><au>Nicolau, Ulisses Ribaldo</au><au>de Lima, Vladmir Cláudio Cordeiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>36</volume><issue>1</issue><spage>8</spage><epage>9</epage><pages>8-9</pages><artnum>8</artnum><issn>1357-0560</issn><issn>1559-131X</issn><eissn>1559-131X</eissn><abstract>There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone (
n
= 37) or chemotherapy with cetuximab (
n
= 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, (
p
= 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (
p
= 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (
p
= 0.002) and a mPFS of 3.2 months versus 4.7 months (
p
= 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08;
p
= 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99;
p
= 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30478503</pmid><doi>10.1007/s12032-018-1234-0</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1631-0105</orcidid></addata></record> |
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source | MEDLINE; SpringerNature Journals |
subjects | Adult Aged Antineoplastic Agents, Immunological - therapeutic use BIOLOGICAL MARKERS Biomarkers, Tumor - analysis CARCINOMAS Cetuximab - therapeutic use CHEMOTHERAPY COMPUTERIZED TOMOGRAPHY Cyclin-Dependent Kinase Inhibitor p18 - metabolism Drug Resistance, Neoplasm - physiology Female HEAD Head & neck cancer Hematology Humans Immunotherapy Internal Medicine Kaplan-Meier Estimate Male Medicine Medicine & Public Health METASTASES Middle Aged Monoclonal antibodies NECK Oncology Original Paper Pathology PATIENTS Prognosis Progression-Free Survival Proportional Hazards Models PROTEINS Proto-Oncogene Proteins c-met - metabolism PTEN Phosphohydrolase - metabolism RADIOLOGY AND NUCLEAR MEDICINE Retrospective Studies Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - drug therapy Squamous Cell Carcinoma of Head and Neck - mortality Targeted cancer therapy |
title | The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma |
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