Research Letter
Thin cutaneous melanoma: immunohistochemical expression of endoglin, VEGF-C and nestin
Maria Carolina Widholzer Reya,
, Adriana Roeheb, Felice Riccardic, Beatriz Silva de Souzad, Mariele Bevilaquaa,e, Renan Rangel Bonamigoa
Corresponding author
a Department of Dermatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
b Department of Pathology and Forensic Medicine, Postgraduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
c Hospital Santa Rita, Santa Casa de Misericórdia de Porto Alegre, Executive Director, Grupo Brasileiro de Melanoma, Porto Alegre, RS, Brazil
d Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
e Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
Read
3805
Timeswas read the article
1579
Total PDF
2226
Total HTML
Share statistics
array:22 [ "pii" => "S0365059622001854" "issn" => "03650596" "doi" => "10.1016/j.abd.2021.11.005" "estado" => "S300" "fechaPublicacion" => "2022-11-01" "aid" => "612" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "pt" => array:17 [ "pii" => "S2666275222001953" "issn" => "26662752" "doi" => "10.1016/j.abdp.2022.09.008" "estado" => "S300" "fechaPublicacion" => "2022-11-01" "aid" => "612" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "pt" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta ‐ Investigação</span>" "titulo" => "Melanoma cutâneo fino: expressão imuno‐histoquímica da endoglina, do VEGF‐C e da nestina" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "814" "paginaFinal" => "816" ] ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1608 "Ancho" => 3341 "Tamanyo" => 856838 ] ] "descripcion" => array:1 [ "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Expressões imuno‐histoquímicas. (A) Nestina (20X). (B) Nestina (40X). (C) Endoglina (40X). (D) Endoglina (40X). (E) VEGF‐C (20X). (F) VEGF‐C (40X).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Maria Carolina Widholzer Rey, Adriana Roehe, Felice Riccardi, Beatriz Silva de Souza, Mariele Bevilaqua, Renan Rangel Bonamigo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Maria Carolina Widholzer" "apellidos" => "Rey" ] 1 => array:2 [ "nombre" => "Adriana" "apellidos" => "Roehe" ] 2 => array:2 [ "nombre" => "Felice" "apellidos" => "Riccardi" ] 3 => array:2 [ "nombre" => "Beatriz Silva de" "apellidos" => "Souza" ] 4 => array:2 [ "nombre" => "Mariele" "apellidos" => "Bevilaqua" ] 5 => array:2 [ "nombre" => "Renan Rangel" "apellidos" => "Bonamigo" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0365059622001854" "doi" => "10.1016/j.abd.2021.11.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622001854?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222001953?idApp=UINPBA00008Z" "url" => "/26662752/0000009700000006/v4_202410140645/S2666275222001953/v4_202410140645/pt/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "S0365059622001775" "issn" => "03650596" "doi" => "10.1016/j.abd.2021.12.004" "estado" => "S300" "fechaPublicacion" => "2022-11-01" "aid" => "605" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>" "titulo" => "Treating hidradenitis suppurativa patients with adalimumab: a real-life experience of a tertiary care center in Lisboa, Portugal" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "816" "paginaFinal" => "819" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Miguel Neves, Nélia Cunha, André Lencastre, Joana Cabete" "autores" => array:4 [ 0 => array:2 [ "nombre" => "José Miguel" "apellidos" => "Neves" ] 1 => array:2 [ "nombre" => "Nélia" "apellidos" => "Cunha" ] 2 => array:2 [ "nombre" => "André" "apellidos" => "Lencastre" ] 3 => array:2 [ "nombre" => "Joana" "apellidos" => "Cabete" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2666275222001886" "doi" => "10.1016/j.abdp.2022.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222001886?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622001775?idApp=UINPBA00008Z" "url" => "/03650596/0000009700000006/v2_202306261757/S0365059622001775/v2_202306261757/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S0365059622001830" "issn" => "03650596" "doi" => "10.1016/j.abd.2021.06.010" "estado" => "S300" "fechaPublicacion" => "2022-11-01" "aid" => "611" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>" "titulo" => "Proteomic study of facial melasma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "808" "paginaFinal" => "814" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2144 "Ancho" => 2508 "Tamanyo" => 376044 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Heat map and dendrograms between identified proteins (rows) and biological functions (columns). Green highlights: grouping of proteins with a similar pattern of occurrence according to the functions they perform; and in red: the functions with a similar expression pattern, according to the indicated proteins.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luiza Vasconcelos Schaefer, Leticia Gomes de Pontes, Nayara Rodrigues Vieira Cavassan, Lucilene Delazari dos Santos, Hélio Amante Miot" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Luiza Vasconcelos" "apellidos" => "Schaefer" ] 1 => array:2 [ "nombre" => "Leticia Gomes de" "apellidos" => "Pontes" ] 2 => array:2 [ "nombre" => "Nayara Rodrigues Vieira" "apellidos" => "Cavassan" ] 3 => array:2 [ "nombre" => "Lucilene Delazari dos" "apellidos" => "Santos" ] 4 => array:2 [ "nombre" => "Hélio Amante" "apellidos" => "Miot" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2666275222001941" "doi" => "10.1016/j.abdp.2022.09.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222001941?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622001830?idApp=UINPBA00008Z" "url" => "/03650596/0000009700000006/v2_202306261757/S0365059622001830/v2_202306261757/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>" "titulo" => "Thin cutaneous melanoma: immunohistochemical expression of endoglin, VEGF-C and nestin" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "814" "paginaFinal" => "816" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Maria Carolina Widholzer Rey, Adriana Roehe, Felice Riccardi, Beatriz Silva de Souza, Mariele Bevilaqua, Renan Rangel Bonamigo" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Maria Carolina Widholzer" "apellidos" => "Rey" "email" => array:1 [ 0 => "caro2rey@yahoo.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Adriana" "apellidos" => "Roehe" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Felice" "apellidos" => "Riccardi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Beatriz Silva de" "apellidos" => "Souza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Mariele" "apellidos" => "Bevilaqua" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Renan Rangel" "apellidos" => "Bonamigo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Dermatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathology and Forensic Medicine, Postgraduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Santa Rita, Santa Casa de Misericórdia de Porto Alegre, Executive Director, Grupo Brasileiro de Melanoma, Porto Alegre, RS, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1608 "Ancho" => 3341 "Tamanyo" => 853770 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemical reactions: A: nestin (20X), B: nestin (40X), C: endoglin (40X), D: endoglin (40X), E: VEGF-C (20X), F: VEGF-C (40X). The chromogen used was 3-amino-9-etilcarbazol (AEC).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The incidence of melanoma is increasing worldwide, and even small, thin tumors can metastasize.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Tumor progression includes proliferation, neovascularization, and lymphangiogenesis,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and many mediators are important in this pathogenesis. Nestin (important in proliferation), endoglin (important in neovascularization), and VEGF-C (important in lymphangiogenesis) have already been described in cutaneous melanoma in general; but with little emphasis on thin melanomas.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe the clinical data of thin melanomas patients with and without metastases and the immunohistochemical expression of nestin, endoglin, and VEGF-C. The project was approved by the Research Ethics Committee of the institution (Counsel number: 332,405).</p><p id="par0015" class="elsevierStylePara elsevierViewall">A case-control study was carried out with 85 patients: 20 patients in the study group and 65 in the control group.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients in the study group were included when they had melanoma metastasis from a thin primary skin lesion (up to 1<span class="elsevierStyleHsp" style=""></span>mm thick). Controls were patients with thin melanoma but without metastasis. Data were collected regarding sex, age, topography, and histopathological subtype of the tumor.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Of the 85 patients, 37 expressed markers (seven in the study group and 30 in the control group). In the study group, three immunohistochemistry reactions were performed for each marker for each patient. In the control group, two reactions were performed for each marker for each patient, aiming at the statistical analysis of data in clusters. Nestin (ABCAM®), Endoglin (CD105; NOVO CASTRA®) and VEGF-C (IN VITRO GEN®) antibodies were used in the standard immunoperoxidase technique. The chromogenic substance was 3-Amino-9-Ethylcarbazole (AEC), as previously used in a prior study of melanoma.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">For endoglin, the lesion hot spots were determined in ×10 magnification fields. Moderate to strong immunohistochemical reactions were considered positive. Up to four hot spots were photographed per slide with ×40 magnification objective. Subsequently, we counted the number of microvessels in each lesion. Areas of fibrosis were avoided, as they could correspond to repair neovascularization instead of neovascularization of the lesion.</p><p id="par0035" class="elsevierStylePara elsevierViewall">To evaluate the differences among the immunohistochemical markers, an analysis based on the Generalized Estimating Equations (GEE) method was used. This technique takes into account the effect of data in clusters, in which a given patient can contribute with a greater number of observations than another. Thus, an adjustment is made for the correlated measures obtained from the same individual. According to the assumptions of data distribution, binding functions per identity (Gaussian), log and Poisson were used.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Regarding the statistical analysis, the quantitative data were described by means and standard error and the categorical variables by counts and percentages. Initial comparisons between groups were performed using Student’s <span class="elsevierStyleItalic">t</span> test or Fisher’s exact test. The level of significance was set at α<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.05; data were entered into an Excel spreadsheet and analyzed using the IBM-SPSS program, version 22.0.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Most patients in the study group were male (75%), whereas, in the control group, 47% of the patients were male. This difference was statistically significant (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.041). The mean age in the study group was 52 years and in the control group, 55 years. In both groups, the most frequent topographic location of the primary melanoma was the trunk. Also in both groups, the most frequent histopathological subtype was superficial spreading melanoma. These data showed no statistical difference (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The immunohistochemical reactions of the markers are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> (A: Nestin, B: Nestin, C: Endoglin, D: Endoglin, E: VEGF-C, F: VEGF-C).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">An immunohistochemical reaction was considered positive for endoglin when moderate to strong. In the study group, the mean number of identified vascular structures was 11.47, with a standard error of 1.27. In the control group, it was 9.22, with a standard error of 0.59. This non-significant difference reached a p-value of 0.088. Nestin and VEGF-C showed no differences between the groups.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The male sex is already known to have a worse prognosis among melanoma patients.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In this study, patients with thin melanoma and metastases were significantly more often male than female.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Nestin, important in cell proliferation, and VEGF-C, important in lymphangiogenesis, have been previously described in cutaneous melanoma in general.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Endoglin (also known as CD105) participates in angiogenesis through endothelial cell proliferation and migration and capillary morphogenesis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The possibility of the involvement of endoglin in the regulation of the biological properties of melanoma cells has been confirmed.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Endoglin expression has been previously detected in melanocytic lesions and in melanoma cell cultures,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> indicating a possible involvement of endoglin in the regulation of the biological properties of melanoma cells.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">It is possible that endoglin participates in the angiogenesis observed in thin melanomas, especially in tumors with metastases, but this study did not provide definitive statistical evidence.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0085" class="elsevierStylePara elsevierViewall">Maria Carolina Widholzer Rey: Design and planning of the study; data collection/analysis and interpretation of data; statistical analysis; drafting of the manuscript or critical review of important intellectual content; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Adriana Roehe: Data collection/analysis and interpretation of data; collection, analysis and interpretation of data; effective participation in research orientation; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Felice Riccardi: Data collection/analysis and interpretation of data; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Beatriz Silva de Souza: Data collection/analysis and interpretation of data; collection, analysis and interpretation of data; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Mariele Bevilaqua: Drafting of the manuscript or critical review of important intellectual content; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Renan Rangel Bonamigo: Design and planning of the study; data collection/analysis and interpretation of data; statistical analysis; drafting of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:2 [ "identificador" => "xack673266" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-08-30" "fechaAceptado" => "2021-11-15" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Postgraduate Program in Pathology and Dermatology, Universidade Federal de Ciências da Saúde de Porto Alegre; Hospital Santa Casa de Porto Alegre, Porto Alegre, RS, Brazil.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1608 "Ancho" => 3341 "Tamanyo" => 853770 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemical reactions: A: nestin (20X), B: nestin (40X), C: endoglin (40X), D: endoglin (40X), E: VEGF-C (20X), F: VEGF-C (40X). The chromogen used was 3-amino-9-etilcarbazol (AEC).</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Data presented as means<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard error or counts (percentages).</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>65) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cases (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.0±11.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.8±15.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.577 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male sex, number (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (47.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.041 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topography, number (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.209 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Trunk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (38.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (70.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Upper limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (27.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lower limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Face \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scalp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Histopathological subtype, number (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.311 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Superficial spreading melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 (86.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (80.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lentigo malignant melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (9.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodular melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acral melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patients general characteristics of controls (melanoma without metastasis) and Cases (melnoma with metastasis).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanoma epidemiology and sun exposure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Raimondi" 1 => "M. Suppa" 2 => "S. Gandini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "2020" "volumen" => "100" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline – update 2016" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Garbe" 1 => "K. Peris" 2 => "A. Hauschild" 3 => "P. Saiag" 4 => "M. Middleton" 5 => "L. Bastholt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejca.2016.05.005" "Revista" => array:6 [ "tituloSerie" => "Eur J Cancer" "fecha" => "2016" "volumen" => "63" "paginaInicial" => "201" "paginaFinal" => "217" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27367293" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural course of cutaneous melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "U. Leiter" 1 => "F. Meier" 2 => "B. Schittek" 3 => "C. Garbe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jso.20079" "Revista" => array:6 [ "tituloSerie" => "J Surg Oncol" "fecha" => "2004" "volumen" => "86" "paginaInicial" => "172" "paginaFinal" => "178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15221923" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MMP-2 and TIMP-2 in cutaneous melanoma: association with prognostic factors and description in cutaneous metastases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.C.W. Rey" 1 => "R.R. Bonamigo" 2 => "A. Cartell" 3 => "R. Furian" 4 => "R. Bonfá" 5 => "R. Bonfá" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/DAD.0b013e3181e2e8d6" "Revista" => array:6 [ "tituloSerie" => "Am J Dermatopathol" "fecha" => "2011" "volumen" => "33" "paginaInicial" => "413" "paginaFinal" => "414" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20966734" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Park" 1 => "C.M. Sorenson" 2 => "N. Sheibani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1042/CS20140714" "Revista" => array:6 [ "tituloSerie" => "Clin Sci (Lond)" "fecha" => "2015" "volumen" => "129" "paginaInicial" => "217" "paginaFinal" => "234" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25976664" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Electrotransfer of plasmid DNA encoding an anti-mouse endoglin (CD105) shRNA to B16 melanoma tumors with low and high metastatic potential results in pronounced anti-tumor effects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Dolinsek" 1 => "G. Sersa" 2 => "L. Prosen" 3 => "M. Bosnjak" 4 => "M. Stimac" 5 => "U. Razborsek" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/cancers8010003" "Revista" => array:5 [ "tituloSerie" => "Cancers (Basel)" "fecha" => "2015" "volumen" => "8" "paginaInicial" => "3" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26712792" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression and structural features of endoglin (CD105), a transforming growth factor β1 and β3 binding protein, in human melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Altomonte" 1 => "R. Montagner" 2 => "E. Fonsatti" 3 => "F. Colizzi" 4 => "I. Cattarossi" 5 => "L.I. Brasoveanu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bjc.1996.593" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "1996" "volumen" => "74" "paginaInicial" => "1586" "paginaFinal" => "1591" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8932339" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack673266" "titulo" => "Acknowledgments" "texto" => "<p id="par0120" class="elsevierStylePara elsevierViewall">We are grateful for the invaluable collaboration of Dr. Mario Wagner and Dr. Tatiana Wittee Neetzow Nunes.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03650596/0000009700000006/v2_202306261757/S0365059622001854/v2_202306261757/en/main.assets" "Apartado" => array:4 [ "identificador" => "82768" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Research Letter" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03650596/0000009700000006/v2_202306261757/S0365059622001854/v2_202306261757/en/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622001854?idApp=UINPBA00008Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 9 | 20 |
| 2024 October | 108 | 65 | 173 |
| 2024 September | 125 | 78 | 203 |
| 2024 August | 131 | 111 | 242 |
| 2024 July | 137 | 98 | 235 |
| 2024 June | 142 | 55 | 197 |
| 2024 May | 142 | 71 | 213 |
| 2024 April | 95 | 88 | 183 |
| 2024 March | 68 | 61 | 129 |
| 2024 February | 87 | 80 | 167 |
| 2024 January | 86 | 61 | 147 |
| 2023 December | 65 | 57 | 122 |
| 2023 November | 69 | 78 | 147 |
| 2023 October | 49 | 65 | 114 |
| 2023 September | 70 | 73 | 143 |
| 2023 August | 53 | 41 | 94 |
| 2023 July | 45 | 22 | 67 |
| 2023 June | 65 | 50 | 115 |
| 2023 May | 47 | 20 | 67 |
| 2023 April | 33 | 18 | 51 |
| 2023 March | 69 | 40 | 109 |
| 2023 February | 61 | 42 | 103 |
| 2023 January | 58 | 48 | 106 |
| 2022 December | 97 | 56 | 153 |
| 2022 November | 100 | 89 | 189 |
| 2022 October | 173 | 77 | 250 |
| 2022 September | 40 | 26 | 66 |
Show all
