Artigo Original/Original Article
Carcinoma epidermóide do pulmão: Polissomia e amplificação do cromossoma 7 e do gene EGRF com forma wild type nos exões 19 e 21
Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type
Patrícia Couceiro1,3, Vítor Sousa1,2,3,4, Ana Alarcão1,3, Maria Silva1,3,4, Lina Carvalho1,2,3,4,
Corresponding author
lcarvalho@huc.min-saude.pt
Correspondência/Correspondence to: Prof. Dra. Lina Carvalho, MD, PhD., Instituto de Anatomia Patológica, Faculdade de Medicina; Universidade de Coimbra, 3000-054 Coimbra, Portugal, Tel. number: 00351239857762/65, Fax number: 00351239857704,
Correspondência/Correspondence to: Prof. Dra. Lina Carvalho, MD, PhD., Instituto de Anatomia Patológica, Faculdade de Medicina; Universidade de Coimbra, 3000-054 Coimbra, Portugal, Tel. number: 00351239857762/65, Fax number: 00351239857704,
1 Instituto de Patologia, Faculdade de Medicina, Universidade do Porto, Portugal/Institute of Pathology, Faculty of Medicine, University of Coimbra, Portugal
2 Serviço de Patologia, Hospitais da Universidade de Coimbra, Portugal/Pathology Service, Coimbra University Hospitals, Portugal
3 CIMAGO, Portugal
4 Serviço de Pneumologia, Hospitais da Universidade de Coimbra, Portugal/Pneumology Center, Coimbra University Hospitals, Portugal
Read
5642
Timeswas read the article
2249
Total PDF
3393
Total HTML
Share statistics
array:24 [ "pii" => "S0873215915300416" "issn" => "08732159" "doi" => "10.1016/S0873-2159(15)30041-6" "estado" => "S350" "fechaPublicacion" => "2010-05-01" "aid" => "7" "copyright" => "Sociedade Portuguesa de Pneumologia/SPP" "copyrightAnyo" => "2010" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2010;16:453-62" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2345 "formatos" => array:3 [ "EPUB" => 225 "HTML" => 1465 "PDF" => 655 ] ] "itemSiguiente" => array:19 [ "pii" => "S0873215915300428" "issn" => "08732159" "doi" => "10.1016/S0873-2159(15)30042-8" "estado" => "S350" "fechaPublicacion" => "2010-05-01" "aid" => "8" "copyright" => "Sociedade Portuguesa de Pneumologia/SPP" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Rev Port Pneumol. 2010;16:463-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2310 "formatos" => array:3 [ "EPUB" => 216 "HTML" => 1425 "PDF" => 669 ] ] "pt" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artigo de Revisão/Review Article</span>" "titulo" => "Papel da pressão inspiratória máxima na avaliação da força muscular respiratória em asmáticos – Revisão sistemática" "tienePdf" => "pt" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "463" "paginaFinal" => "470" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Role of maximal inspiratory presure in the evaluetion of respiratory muscle strength in asthmatics – Systematic review" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alessandra M.F. Cavalcante Marcelino, Hilton Justino da Silva" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alessandra M.F." "apellidos" => "Cavalcante Marcelino" ] 1 => array:2 [ "nombre" => "Hilton Justino" "apellidos" => "da Silva" ] ] ] ] ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215915300428?idApp=UINPBA00004E" "url" => "/08732159/0000001600000003/v1_201509151447/S0873215915300428/v1_201509151447/pt/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0873215915300404" "issn" => "08732159" "doi" => "10.1016/S0873-2159(15)30040-4" "estado" => "S350" "fechaPublicacion" => "2010-05-01" "aid" => "6" "copyright" => "Sociedade Portuguesa de Pneumologia/SPP" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2010;16:431-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2387 "formatos" => array:3 [ "EPUB" => 229 "HTML" => 1551 "PDF" => 607 ] ] "pt" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artigo Original/Original Article</span>" "titulo" => "Reacções adversas aos antibacilares em doentes internados: Gravidade e factores de risco" "tienePdf" => "pt" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "431" "paginaFinal" => "451" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Adverse reactions to antituberculosis drugs in in-hospital patients: Severity and risk factors" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Sofia Vilariça, Nelson Diogo, Mota André, Jaime Pina" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ana Sofia" "apellidos" => "Vilariça" ] 1 => array:2 [ "nombre" => "Nelson" "apellidos" => "Diogo" ] 2 => array:2 [ "nombre" => "Mota" "apellidos" => "André" ] 3 => array:2 [ "nombre" => "Jaime" "apellidos" => "Pina" ] ] ] ] ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215915300404?idApp=UINPBA00004E" "url" => "/08732159/0000001600000003/v1_201509151447/S0873215915300404/v1_201509151447/pt/main.assets" ] "pt" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artigo Original/Original Article</span>" "titulo" => "Carcinoma epidermóide do pulmão: Polissomia e amplificação do cromossoma 7 e do gene EGRF com forma <span class="elsevierStyleItalic">wild type</span> nos exões 19 e 21" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "453" "paginaFinal" => "462" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Patrícia Couceiro, Vítor Sousa, Ana Alarcão, Maria Silva, Lina Carvalho" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Patrícia" "apellidos" => "Couceiro" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] ] ] 1 => array:3 [ "nombre" => "Vítor" "apellidos" => "Sousa" "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "af0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">4</span>" "identificador" => "af0020" ] ] ] 2 => array:3 [ "nombre" => "Ana" "apellidos" => "Alarcão" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] ] ] 3 => array:3 [ "nombre" => "Maria" "apellidos" => "Silva" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">4</span>" "identificador" => "af0020" ] ] ] 4 => array:4 [ "nombre" => "Lina" "apellidos" => "Carvalho" "email" => array:1 [ 0 => "lcarvalho@huc.min-saude.pt" ] "referencia" => array:5 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "af0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">4</span>" "identificador" => "af0020" ] 4 => array:2 [ "etiqueta" => "*" "identificador" => "cr0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Instituto de Patologia, Faculdade de Medicina, Universidade do Porto, Portugal/Institute of Pathology, Faculty of Medicine, University of Coimbra, Portugal" "etiqueta" => "1" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Serviço de Patologia, Hospitais da Universidade de Coimbra, Portugal/Pathology Service, Coimbra University Hospitals, Portugal" "etiqueta" => "2" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "CIMAGO, Portugal" "etiqueta" => "3" "identificador" => "af0015" ] 3 => array:3 [ "entidad" => "Serviço de Pneumologia, Hospitais da Universidade de Coimbra, Portugal/Pneumology Center, Coimbra University Hospitals, Portugal" "etiqueta" => "4" "identificador" => "af0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "*" "correspondencia" => "<span class="elsevierStyleBold">Correspondência/<span class="elsevierStyleItalic">Correspondence to:</span></span> Prof. Dra. Lina Carvalho, MD, PhD., Instituto de Anatomia Patológica, Faculdade de Medicina; Universidade de Coimbra, 3000-054 Coimbra, Portugal, Tel. number: 00351239857762/65, Fax number: 00351239857704," ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-09-18" "fechaAceptado" => "2009-10-07" "PalabrasClave" => array:2 [ "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec570166" "palabras" => array:6 [ 0 => "Carcinoma do pulmão" 1 => "carcinoma epidermóide" 2 => "tecido incluído em parafina" 3 => "EGFR" 4 => "amplificação" 5 => "polissomia" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key-words" "identificador" => "xpalclavsec570167" "palabras" => array:6 [ 0 => "Lung cancer" 1 => "epidermoid carcinoma" 2 => "paraffin-embedded tissue" 3 => "EGFR" 4 => "gene amplification" 5 => "gene polysomy" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Objectivo:</span> O receptor do factor de crescimento epidérmico (EGFR) está sobreexpresso na maioria dos carcinomas do pulmão de não pequenas células (CPNPC) e é um dos principais alvos específicos dos inibidores da tirosina cinase (TKI) utilizados para o tratamento do CPNPC avançado. Apesar disto, há um considerável número de factores biológicos que também estão associados à resposta dos EGFR-TKIs. Este estudo teve como principal objectivo a pesquisa de mutações somáticas e amplificação do <span class="elsevierStyleItalic">EGFR</span> em casos de carcinoma epidermóide do pulmão. <span class="elsevierStyleBold">Material e métodos:</span> Secções representativas de carcinoma epidermóide foram seleccionadas de 54 casos em que o tecido estava fixado em formal e incluído em parafina, sendo depois submetidos à construção de TMA. A determinação da expressão proteica do EGFR foi feita por imunoistoquímica (IHQ) (Zymed, laboratórios). A hibridização <span class="elsevierStyleItalic">in situ</span> de fluorescência (FISH) foi realizada com a sonda EGFR LSI / CEP 7 (Vysis; Abbott Molecular, EUA). O ADN genómico foi extraído de 48 casos, amplificado por reacção em cadeia da polimerase (PCR) para pesquisa de mutações nos exões 19 (deleções) e 21 (mutações pontuais). Todos os casos expressaram positividade para a citoqueratina de alto peso molecular e foi observada negatividade para CK7, CD56 e cromogranina. <span class="elsevierStyleBold">Resultados:</span> A sobreexpressão proteica do EGFR foi identificada em 49 casos, pela aplicação do <span class="elsevierStyleItalic">score</span> de Hirsh/ Cappuzzo (2005). A pesquisa de alterações génicas no cromossoma 7 e do gene <span class="elsevierStyleItalic">EGFR</span> foram analisadas por FISH e de acordo com o método de Cappuzzo (2005), foi identificada alta polissomia em 31 casos e amplificação em 7 casos. Por electroforese capilar, foram detectadas no exão 19 do <span class="elsevierStyleItalic">EGFR</span>: deleções em heterozigotia em 3 dos 48 casos estudados e o exão 21 apresentou-se sempre na sua forma <span class="elsevierStyleItalic">wild-type</span>, quando estudado por enzimas de restrição. <span class="elsevierStyleBold">Conclusões:</span> A detecção de deleções e mutações pontuais no <span class="elsevierStyleItalic">EGFR</span> mostrou ser um evento raro no carcinoma epidermóide do pulmão. Apesar de a presença de mutações no <span class="elsevierStyleItalic">EGFR</span> ser um indicador molecular e de sensibilidade eficaz em doentes com CPNPC avançado, submetidos ao tratamento com EGFR-TKIs, é a determinação de amplificações e de polissomias no gene <span class="elsevierStyleItalic">EGFR</span> que melhor traduz a eficácia do tratamento nos doentes com carcinoma epidermóide, quando isolado do grupo de CPNPC.</p><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2010; XVI (3): 453-462</span></p></span>" ] "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Purpose:</span> The epidermal growth factor receptor (EGFR) is overexpressed in the majority of nonsmall-cell lung cancers (NSCLC) and is a major target specific EGFR tyrosine kinase inhibitors (TKIs) developed and used for the treatment of advanced NSCLC. A number of biological factors are also associated with EGFR-TKIs responsiveness. This study was focused on EGFR somatic mutations and amplifications in squamous cell lung cancer. <span class="elsevierStyleBold">Material and methods:</span> Representative sections of squamous cell carcinoma were selected from 54 surgical specimens from formalin-fixed paraffin-embedded tissues and submitted to TMA construction. Determination of EGFR protein expression was done by immuno-histochemistry(IHC) (Zymed, Laboratories). Fluorescence <span class="elsevierStyleItalic">in situ</span> hybridization (FISH) was performed with LSI EGFR/CEP 7 (<span class="elsevierStyleItalic">Vysis</span>; Abbott Molecular, USA). Genomic DNA was extracted from 48 cases and exon 19 was amplified by polymerase chain reaction (PCR) for search deletions and point mutations for exon 21. All cases expressed high weigh cytokeratin and were observed negativity for CK7, CD56 and chromogranin. <span class="elsevierStyleBold">Results:</span> EGFR protein overexpression was identified in 49 cases, by the application of Hirsh’s scoring system. The chromosome 7 and EGFR gene were analyzed by FISH and scored according to Cappuzzo’s method that showed high polysomy in 31 cases and amplification in 7 cases. Deletion in exon 19 of EGFR was detected in 3 cases of 48 samples; the exon 21 of EGFR was expressed in its wild type by RFLP in all cases. <span class="elsevierStyleBold">Conclusions:</span> Detection of common EGFR deletion and mutation showed to be a rare event in Squamous cell carcinoma of the lung. While EGFR mutation is the most effective molecular predictor or sensitivity in patients with advanced NSCLC submitted to EGFR-TKIs treatment, amplification and polysomy is the most effective molecular predictor for EGFR-TKIs responsiveness in squamous cell carcinoma, when validated isolated from the group of NSCLC.</p><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2010; XVI (3): 453-462</span></p></span>" ] ] "lecturaRecomendada" => array:1 [ 0 => array:3 [ "vista" => "all" "titulo" => "<span class="elsevierStyleSectionTitle" id="st0030">Biblilography</span>" "seccion" => array:1 [ 0 => array:2 [ "vista" => "all" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular predictors of EGFR sensitivity in advanced non-small cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "X. Zhang" 1 => "A. Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Int J Med Sci" "fecha" => "2008" "volumen" => "5" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sunaga N, Tomizawa Y, Yanagitani N, et al. Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small-cell lung cancer with EGFR mutations, irrespective." ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:2 [ 0 => "M. Toyooka S. Tokumo" 1 => "K. Kiura" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2005" "volumen" => "11" "paginaInicial" => "1167" "paginaFinal" => "1173" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15709185" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular predictors of response to epidermal growth factor receptor antagonists in non-small cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.V. Sequist" 1 => "D.W. Bell" 2 => "T.J. Lynch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2006.07.3585" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "587" "paginaFinal" => "595" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17290067" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bb0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update molecular analyses of exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene and codons 12 and 13 of KRAS gene in non-small-cell lung cancer (NSCLC) patients treated with erlotinib in National Cancer Insti tute of Cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F.A. Shepherd" 1 => "K. Ding" 2 => "A. Sakurada" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "402s" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bb0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Inoue" 1 => "S. Tatsuro" 2 => "M. Maemondo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2005.05.4692" "Revista" => array:7 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2006" "volumen" => "24" "numero" => "21" "paginaInicial" => "3340" "paginaFinal" => "3346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16785471" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective validation for prediction of gefitinib sensivity by epidermal growth factor receptor gene mutation in patients with non-smallcell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "K. Yoshida" 1 => "Y. Yatabe" 2 => "J.Y. Park" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/JTO.0b013e31811f472a" "Revista" => array:5 [ "tituloSerie" => "J Thorac Oncol" "fecha" => "2007" "volumen" => "2" "numero" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17805058" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bb0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro and prospective observations in non-small-cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Zandwijk van" 1 => "A. Mathy" 2 => "L. Boerrigter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdl323" "Revista" => array:6 [ "tituloSerie" => "Annals of Oncology" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "99" "paginaFinal" => "103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17060486" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bb0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "X. Zhang" 1 => "A. Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2006.046102" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2007" "volumen" => "44" "paginaInicial" => "166" "paginaFinal" => "172" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17158592" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bb0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical course of patients with non-small-cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Cancer therapy: Clinical" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G.J. Riely" 1 => "W. Pao" 2 => "D. Pham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-06-1315" "Revista" => array:5 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2006" "volumen" => "12" "numero" => "3" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17085654" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bb0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidermal growth factor receptor gene amplification and gefitinib sensivity in patients with recurrent lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Sasaki" 1 => "K. Endo" 2 => "K. Okuda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00432-007-0320-z" "Revista" => array:6 [ "tituloSerie" => "J Cancer Res Clin Oncol" "fecha" => "2008" "volumen" => "134" "paginaInicial" => "569" "paginaFinal" => "577" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17932690" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bb0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-smallcell lung cancer patients treated with gefitinib" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F.R. Hirsh" 1 => "M. Varella-Garcia" 2 => "F. Cappuzzo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdm003" "Revista" => array:6 [ "tituloSerie" => "Annals of Oncology" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "752" "paginaFinal" => "760" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17317677" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bb0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EGFR and HER2 gene copy number and response to first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Cappuzzo" 1 => "F.R. Hirsh" 2 => "C. Ligorio" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Thor Oncol" "fecha" => "2007" "volumen" => "2" "numero" => "5" "paginaInicial" => "423" "paginaFinal" => "429" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bb0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ErbB receptor tyrosine family as signal integrators" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N.E. Hynes" 1 => "K. Horsch" 2 => "M.A. Olayioye" 3 => "A. Badache" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:8 [ "tituloSerie" => "Endocr Relat Cancer" "fecha" => "2001" "volumen" => "8" "numero" => "3" "paginaInicial" => "151" "paginaFinal" => "159" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11566606" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0210480609740094" "estado" => "S300" "issn" => "02104806" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bb0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hynes NE The ErbB receptors and their role in cancer progression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Holbro" 1 => "G. Civenni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Exp Cell Res" "fecha" => "2003" "volumen" => "284" "numero" => "1" "paginaInicial" => "99" "paginaFinal" => "110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12648469" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "pt" "url" => "/08732159/0000001600000003/v1_201509151447/S0873215915300416/v1_201509151447/pt/main.assets" "Apartado" => array:4 [ "identificador" => "9575" "tipo" => "SECCION" "pt" => array:2 [ "titulo" => "Artigos originais" "idiomaDefecto" => true ] "idiomaDefecto" => "pt" ] "PDF" => "https://static.elsevier.es/multimedia/08732159/0000001600000003/v1_201509151447/S0873215915300416/v1_201509151447/pt/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215915300416?idApp=UINPBA00004E" ]
Article information
ISSN: 08732159Original language: Portuguese
The statistics are updated each day
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 4 | 10 |
| 2024 October | 49 | 41 | 90 |
| 2024 September | 49 | 25 | 74 |
| 2024 August | 49 | 42 | 91 |
| 2024 July | 38 | 36 | 74 |
| 2024 June | 40 | 36 | 76 |
| 2024 May | 33 | 40 | 73 |
| 2024 April | 37 | 30 | 67 |
| 2024 March | 44 | 35 | 79 |
| 2024 February | 31 | 28 | 59 |
| 2024 January | 22 | 27 | 49 |
| 2023 December | 25 | 30 | 55 |
| 2023 November | 20 | 23 | 43 |
| 2023 October | 22 | 26 | 48 |
| 2023 September | 25 | 34 | 59 |
| 2023 August | 23 | 24 | 47 |
| 2023 July | 26 | 30 | 56 |
| 2023 June | 21 | 22 | 43 |
| 2023 May | 33 | 25 | 58 |
| 2023 April | 34 | 19 | 53 |
| 2023 March | 31 | 33 | 64 |
| 2023 February | 23 | 18 | 41 |
| 2023 January | 32 | 22 | 54 |
| 2022 December | 29 | 17 | 46 |
| 2022 November | 44 | 39 | 83 |
| 2022 October | 40 | 23 | 63 |
| 2022 September | 29 | 33 | 62 |
| 2022 August | 43 | 37 | 80 |
| 2022 July | 22 | 34 | 56 |
| 2022 June | 21 | 29 | 50 |
| 2022 May | 39 | 41 | 80 |
| 2022 April | 27 | 29 | 56 |
| 2022 March | 24 | 42 | 66 |
| 2022 February | 27 | 28 | 55 |
| 2022 January | 23 | 32 | 55 |
| 2021 December | 26 | 34 | 60 |
| 2021 November | 26 | 32 | 58 |
| 2021 October | 34 | 45 | 79 |
| 2021 September | 31 | 33 | 64 |
| 2021 August | 23 | 27 | 50 |
| 2021 July | 29 | 27 | 56 |
| 2021 June | 20 | 31 | 51 |
| 2021 May | 28 | 24 | 52 |
| 2021 April | 43 | 69 | 112 |
| 2021 March | 42 | 12 | 54 |
| 2021 February | 47 | 19 | 66 |
| 2021 January | 30 | 24 | 54 |
| 2020 December | 31 | 12 | 43 |
| 2020 November | 44 | 19 | 63 |
| 2020 October | 26 | 15 | 41 |
| 2020 September | 55 | 18 | 73 |
| 2020 August | 51 | 31 | 82 |
| 2020 July | 69 | 18 | 87 |
| 2020 June | 45 | 16 | 61 |
| 2020 May | 49 | 20 | 69 |
| 2020 April | 46 | 16 | 62 |
| 2020 March | 39 | 10 | 49 |
| 2020 February | 32 | 32 | 64 |
| 2020 January | 32 | 16 | 48 |
| 2019 December | 37 | 20 | 57 |
| 2019 November | 47 | 17 | 64 |
| 2019 October | 32 | 12 | 44 |
| 2019 September | 40 | 26 | 66 |
| 2019 August | 49 | 19 | 68 |
| 2019 July | 40 | 16 | 56 |
| 2019 June | 25 | 10 | 35 |
| 2019 May | 30 | 38 | 68 |
| 2019 April | 47 | 36 | 83 |
| 2019 March | 68 | 10 | 78 |
| 2019 February | 65 | 12 | 77 |
| 2019 January | 63 | 24 | 87 |
| 2018 December | 27 | 10 | 37 |
| 2018 November | 3 | 1 | 4 |
| 2018 October | 7 | 8 | 15 |
| 2018 September | 21 | 8 | 29 |
| 2018 August | 50 | 25 | 75 |
| 2018 July | 31 | 29 | 60 |
| 2018 June | 44 | 20 | 64 |
| 2018 May | 49 | 17 | 66 |
| 2018 April | 51 | 29 | 80 |
| 2018 March | 49 | 29 | 78 |
| 2018 February | 49 | 5 | 54 |
| 2018 January | 59 | 10 | 69 |
| 2017 December | 59 | 15 | 74 |
| 2017 November | 45 | 23 | 68 |
| 2017 October | 30 | 22 | 52 |
| 2017 September | 27 | 17 | 44 |
| 2017 August | 24 | 12 | 36 |
| 2017 July | 14 | 11 | 25 |
| 2017 June | 21 | 12 | 33 |
| 2017 May | 33 | 8 | 41 |
| 2017 April | 14 | 4 | 18 |
| 2017 March | 14 | 2 | 16 |
| 2017 February | 10 | 4 | 14 |
| 2017 January | 18 | 3 | 21 |
| 2016 December | 14 | 6 | 20 |
| 2016 November | 12 | 3 | 15 |
| 2016 October | 15 | 7 | 22 |
| 2016 September | 13 | 1 | 14 |
| 2016 August | 6 | 2 | 8 |
| 2016 July | 4 | 5 | 9 |
| 2016 June | 3 | 0 | 3 |
| 2016 May | 13 | 0 | 13 |
| 2016 April | 3 | 3 | 6 |
| 2016 March | 8 | 8 | 16 |
| 2016 February | 8 | 4 | 12 |
| 2016 January | 9 | 4 | 13 |
| 2015 December | 9 | 3 | 12 |
| 2015 November | 3 | 2 | 5 |
| 2015 October | 2 | 3 | 5 |
Show all
