ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma
Oral squamous cell carcinoma (OSCC) is one of the most common cancer in the head and neck and results in high morbidity and mortality annually, being the worst prognosis related to the presence of metastasis in cervical lymph nodes. Metastasis has been associated with a subpopulation of tumor cells,...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis de maestría |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | Brasil |
| Institución: | Universidade de São Paulo (USP) |
| Repositorio: | Biblioteca Digital de Teses e Dissertações da USP |
| Idioma: | inglés |
| OAI Identifier: | oai:teses.usp.br:tde-16122021-094529 |
| Acceso en línea: | https://www.teses.usp.br/teses/disponiveis/25/25149/tde-16122021-094529/ |
| Access Level: | acceso abierto |
| Palabra clave: | ALDH1 Cancer Stem Cells Carcinoma epidermóide de boca CD44 Células-tronco de câncer Cervical metastatic lymph node linfonodo cervical metastático Oral Squamous Cell Carcinoma |
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ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma Immunoexpressão de ALDH1 e CD44 como indicador de prognóstico de invasão e metástase em carcinoma epidermoide de boca |
| title |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| spellingShingle |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma Ortiz, Rafael Carneiro ALDH1 ALDH1 Cancer Stem Cells Carcinoma epidermóide de boca CD44 CD44 Células-tronco de câncer Cervical metastatic lymph node linfonodo cervical metastático Oral Squamous Cell Carcinoma |
| title_short |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| title_full |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| title_fullStr |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| title_full_unstemmed |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| title_sort |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma |
| dc.creator.none.fl_str_mv |
Ortiz, Rafael Carneiro |
| author |
Ortiz, Rafael Carneiro |
| author_facet |
Ortiz, Rafael Carneiro |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Pegoraro, Camila de Oliveira Rodini |
| dc.subject.por.fl_str_mv |
ALDH1 ALDH1 Cancer Stem Cells Carcinoma epidermóide de boca CD44 CD44 Células-tronco de câncer Cervical metastatic lymph node linfonodo cervical metastático Oral Squamous Cell Carcinoma |
| topic |
ALDH1 ALDH1 Cancer Stem Cells Carcinoma epidermóide de boca CD44 CD44 Células-tronco de câncer Cervical metastatic lymph node linfonodo cervical metastático Oral Squamous Cell Carcinoma |
| description |
Oral squamous cell carcinoma (OSCC) is one of the most common cancer in the head and neck and results in high morbidity and mortality annually, being the worst prognosis related to the presence of metastasis in cervical lymph nodes. Metastasis has been associated with a subpopulation of tumor cells, called cancer stem cells (CSCs), which consists of a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to other ordinary tumor cells from the tumor bulk. The aim of present study was to evaluate the immunoexpression of the CSC markers ALDH1 and CD44 in primary sites of OSCC and corresponding metastatic lymph nodes, by means of immunohistochemistry. The immunolabeling was further correlated with clinicopathological data. Archived Formalin-fixed, Paraffin-embedded tumor tissue specimens (n=50) and corresponding metastatic lymph nodes (n=25) were obtained from 50 patients with OSCC after surgical treatment. CD44 and ALDH1 immunostaining were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic cervical lymph nodes as a whole. The percentage of ALDH1 and CD44 positive tumor cells as well as immunostaining intensity was graded and a combined score, ranging from 0 to 9 (ALDH1) or 0 to 12 (CD44), was obtained by multiplying both parameters. Next, combined scores were dichotomized into a final score classified as low (ALDH1 2; CD44 4) or high (ALDH1> 2; CD44> 4) immunoexpression. ALDH1 and CD44 immunoexpression was detected in both primary and metastatic tumor sites, although with different immunolabeling pattern. ALDH1-positive tumor cells consisted of scattered patches and no immunoexpression was observed within keratin pearls. Conversely, CD44 immunopositivity was more homogeneous and widely distributed, with higher labeling in peripheral areas of the tumor islands within the tumor invasion front. Although not statistically significant, the means of ALDH1high (p= 0.0985) and CD44high (p= 0.1632; Mann- Whitney post-test) immunoexpression were higher in metastatic lymph nodes compared to primary tumors. ALDH1high was positively associated (p= 0.0184) with perivascular invasion, while CD44high was positively associated (p= 0.0186; Fishers Exact Test) with metastasis (N+). Five-year survival rates tended to be lower in patients with ALDH1high immunoexpression compared to ALDH1low, although with no statistical significance (p= 0.1303). In summary, the present study revealed that CD44 is highly labeled in tumor cell from metastatic sites, being associated with lymph node metastasis, while ALDH1 high immunostaining was associated with perivascular invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with OSCC invasion and metastasis. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017-10-04 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| format |
masterThesis |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
https://www.teses.usp.br/teses/disponiveis/25/25149/tde-16122021-094529/ |
| url |
https://www.teses.usp.br/teses/disponiveis/25/25149/tde-16122021-094529/ |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
|
| dc.rights.driver.fl_str_mv |
Liberar o conteúdo para acesso público. info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Liberar o conteúdo para acesso público. |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.coverage.none.fl_str_mv |
|
| dc.publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
| publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
| dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da USP instname:Universidade de São Paulo (USP) instacron:USP |
| instname_str |
Universidade de São Paulo (USP) |
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USP |
| institution |
USP |
| reponame_str |
Biblioteca Digital de Teses e Dissertações da USP |
| collection |
Biblioteca Digital de Teses e Dissertações da USP |
| repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP) |
| repository.mail.fl_str_mv |
virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br |
| _version_ |
1853670200502648832 |
| spelling |
ALDH1 and CD44 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinomaImmunoexpressão de ALDH1 e CD44 como indicador de prognóstico de invasão e metástase em carcinoma epidermoide de bocaALDH1ALDH1Cancer Stem CellsCarcinoma epidermóide de bocaCD44CD44Células-tronco de câncerCervical metastatic lymph nodelinfonodo cervical metastáticoOral Squamous Cell CarcinomaOral squamous cell carcinoma (OSCC) is one of the most common cancer in the head and neck and results in high morbidity and mortality annually, being the worst prognosis related to the presence of metastasis in cervical lymph nodes. Metastasis has been associated with a subpopulation of tumor cells, called cancer stem cells (CSCs), which consists of a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to other ordinary tumor cells from the tumor bulk. The aim of present study was to evaluate the immunoexpression of the CSC markers ALDH1 and CD44 in primary sites of OSCC and corresponding metastatic lymph nodes, by means of immunohistochemistry. The immunolabeling was further correlated with clinicopathological data. Archived Formalin-fixed, Paraffin-embedded tumor tissue specimens (n=50) and corresponding metastatic lymph nodes (n=25) were obtained from 50 patients with OSCC after surgical treatment. CD44 and ALDH1 immunostaining were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic cervical lymph nodes as a whole. The percentage of ALDH1 and CD44 positive tumor cells as well as immunostaining intensity was graded and a combined score, ranging from 0 to 9 (ALDH1) or 0 to 12 (CD44), was obtained by multiplying both parameters. Next, combined scores were dichotomized into a final score classified as low (ALDH1 2; CD44 4) or high (ALDH1> 2; CD44> 4) immunoexpression. ALDH1 and CD44 immunoexpression was detected in both primary and metastatic tumor sites, although with different immunolabeling pattern. ALDH1-positive tumor cells consisted of scattered patches and no immunoexpression was observed within keratin pearls. Conversely, CD44 immunopositivity was more homogeneous and widely distributed, with higher labeling in peripheral areas of the tumor islands within the tumor invasion front. Although not statistically significant, the means of ALDH1high (p= 0.0985) and CD44high (p= 0.1632; Mann- Whitney post-test) immunoexpression were higher in metastatic lymph nodes compared to primary tumors. ALDH1high was positively associated (p= 0.0184) with perivascular invasion, while CD44high was positively associated (p= 0.0186; Fishers Exact Test) with metastasis (N+). Five-year survival rates tended to be lower in patients with ALDH1high immunoexpression compared to ALDH1low, although with no statistical significance (p= 0.1303). In summary, the present study revealed that CD44 is highly labeled in tumor cell from metastatic sites, being associated with lymph node metastasis, while ALDH1 high immunostaining was associated with perivascular invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with OSCC invasion and metastasis.O carcinoma epidermóide de boca (CEB) é uma das neoplasias mais comuns da região de cabeça e pescoço e resulta em alta morbidade e mortalidade anualmente, estando o pior prognóstico relacionado à presença de metástase em linfonodos cervicais. O processo de metástase tem sido associado a uma subpopulação de células tumorais, chamadas células-tronco de câncer (CSC, do inglês Cancer stem cells), que consistem em uma pequena população de células com propriedades de células-tronco, incluindo maior taxa de migração e potencial metastático em comparação com outras células tumorais. O objetivo do presente estudo foi avaliar os marcadores candidatos de CSCs ALDH1 e CD44 em tumores primários de CEB e metástases linfonodais correspondentes, por meio de imuno-histoquímica. A imunomarcação foi posteriormente correlacionada com dados clínico-patológicos. Foram obtidas amostras de tecido tumoral parafinado fixado em formalina (n = 50) e os linfonodos metastáticos correspondentes (n = 25) de 50 pacientes com CEB submetidos somente ao tratamento cirúrgico. Os marcadores CD44 e ALDH1 foram analisados de forma semi-quantitativa de acordo com a proporção e intensidade de células positivas no fronte de invasão e em linfonodos cervicais metastáticos como um todo. A porcentagem de células tumorais ALDH1 e CD44 positivas, bem como a intensidade da imunomarcação, foi classificada em um escore combinado obtido pela multiplicação de ambos os parâmetros, variando de 0 a 9 (ALDH1) ou 0 a 12 (CD44). Em seguida, as pontuações combinadas foram dicotomizadas em um escore final classificado como baixo (do inglês low) (ALDH1 2; CD44 4) ou alto (do inglês high) (ALDH1> 2; CD44> 4). A imunoexpressão de ALDH1 e CD44 foi detectada tanto em tumores primários quanto em linfonodos cervicais metastáticos, embora com padrão diferente de imunomarcação. Células tumorais ALDH1-positivas foram identificadas como focais e dispersas ao longo do fronte de invasão, sem imunomarcação nas pérolas córneas. Em contraste, a imunopositividade para CD44 foi mais homogênea e amplamente distribuída, com maior imunomarcação em áreas periféricas das ilhotas tumorais presentes no fronte de invasão. Embora não estatisticamente significativa, as médias da imunoexpressão ALDH1high (p = 0.0985) e CD44high (p = 0.1632, pós-teste de Mann-Whitney) foram maiores em linfonodos metastáticos em comparação com tumores primários. ALDH1high foi positivamente associado com invasão perivascular (p = 0.0184), enquanto CD44high foi com metástase (N+) (p = 0.0186; teste exato de Fisher). As taxas de sobrevida global em 5 anos tenderam a ser mais baixas em pacientes com imunoexpressão elevada de ALDH1 em comparação com ALDH1low, embora sem significância estatística (p = 0.1303). Em resumo, o presente estudo revelou que a elevada imunomarcação de CD44 está significativamente associada com metástases linfonodais, enquanto que a elevada imunomarcação de ALDH1 está associada com invasão perivascular. Em conjunto, sugerimos que a imunoexpressão de CD44 e ALDH1 esteja relacionada com o fenótipo de células tronco de câncer que tem capacidade de invasão e metástase em CEB.Biblioteca Digitais de Teses e Dissertações da USPPegoraro, Camila de Oliveira Rodini2017-10-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/25/25149/tde-16122021-094529/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccessengOrtiz, Rafael Carneiro2024-08-15T19:47:03Zoai:teses.usp.br:tde-16122021-094529Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212024-08-15T19:47:03Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false |
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15.300719 |