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Master's Dissertation
DOI
10.11606/D.25.2011.tde-27072011-095304
Document
Author
Full name
Diego Mauricio Bravo Calderón
Institute/School/College
Knowledge Area
Date of Defense
Published
Bauru, 2011
Supervisor
Committee
Oliveira, Denise Tostes (President)
Pereira, Michele Conceição
Santos, Paulo Sergio da Silva
Title in Portuguese
Expressão de receptor beta-2 adrenérgico em carcinoma espinocelular de boca e sua associação com a evolução clínica tumoral
Keywords in Portuguese
Câncer de boca
Estresse
Receptor β2 adrenérgico
Abstract in Portuguese
Os hormônios produzidos durante o estresse e seus receptores específicos têm sido amplamente envolvidos com a progressão do câncer. O objetivo deste estudo foi avaliar a expressão dos receptores β2 adrenérgicos pelas células malignas de carcinomas espinocelulares de boca (CEC) e sua correlação com as a características clínicas, evolução e o prognóstico dos pacientes. Um total de 106 pacientes portadores de CEC de boca em estádios clínicos II, III e IV, tratados no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital de Câncer A.C. Camargo, São Paulo, Brasil, no período de 1970 a 2000, foram analisados quanto aos dados demográficos, história clínica, localização e extensão do tumor, classificação pelo sistema TNM-UICC, tratamento e evolução tumoral. Analisaram-se também as características histopatológicas, índice de malignidade tumoral e a expressão imuno-histoquímica do receptor β2 adrenérgico pelas células malignas no front de invasão tumoral. A associação da expressão do receptor β2 adrenérgico e as variáveis clínicas ou microscópicas foi calculada pelo teste do qui quadrado ou teste exato de Fisher. As probabilidades de sobrevida global e específica por câncer em 5 e 10 anos foram calculadas pelo estimador produto-limite de Kaplan-Meier, comparadas pelo test de long-rank e pelo modelo de regressão múltiplo de Cox. A expressão do receptor β2 adrenérgico foi detectada na membrana e no citoplasma das células malignas da maioria dos CECs de boca (72,6%) e, significativamente associada ao etilismo (p=0,021), tabagismo e etilismo simultâneo (p=0,014) e estadiamento T (p=0,07). Os pacientes cujos tumores demonstraram expressão positiva do receptor β2 adrenérgico apresentaram maiores taxas de sobrevida global (p=0,001) e específica por câncer (p=0,004), quando comparadas aquelas dos pacientes com tumores com ausência da expressão desta proteína. Esses resultados sugerem que a expressão do receptor β2 adrenérgico nas células malignas da região do front de invasão tumoral constitui um fator prognóstico favorável em pacientes com carcinoma espinocelular de boca e pode ser utilizada como alvo de novas estratégias farmacológicas antineoplásicas.
Title in English
Expression of beta-2 adrenergic receptor in oral squamous cell carcinoma and its association with tumor clinical outcome
Keywords in English
β2 adrenergic receptor
Oral cancer
Stress
Abstract in English
The stress related hormones and their specific receptors have been widely involved with cancer progression. The aim of this study was to evaluate the expression of β2 adrenergic receptor by malignant cells in oral squamous cell carcinoma (OSCC) and its correlation with clinical characteristics, outcome and patients prognosis. A total of 106 patients with OSCC in clinical stages II, III and IV submitted to surgical treatment at the Head and Neck Surgery and Otorhinolaryngology Department, of the Cancer Hospital A.C. Camargo, São Paulo, Brazil, from 1970 to 2000, were analyzed for demographics data, clinical history, location, tumor extension, stage by the TNM-UICC, treatment and tumor outcome. In addition, we investigated the morphologic features, the histopathological malignant index and the immunohistochemical expression of β2 adrenergic receptor by malignant cells of the invasive front of tumor. Chi-square test or Fishers exact test was used to analyze the association among β2 adrenergic receptor expression and the clinical or morphologic variables. The probability of overall and cancer specific survival in 5 and 10 years were calculated by Kaplan-Meier method and the prognostic value of the clinical and morphologic variables was obtained by Cox regression model. Most of OSCCs (72,6%) showed the β2 adrenergic receptor expression in cytoplasm and cell membrane of malignant cells. In OSCC, positive β2 adrenergic receptor expression was significantly associated with alcoholism (p=0.021), simultaneous consumption of alcohol and tobacco (p=0.014) and T stage (p=0.07). OSCC patients with positive expression of β2 adrenergic receptor showed higher rates of overall survival (p=0.001) and cancer specific (p=0.004) than those patients with tumors without expression of this protein. These results suggest that the β2 adrenergic receptor expression by malignant cells in the invasive front of tumor is a favorable prognostic factor in patients with OSCC and can be used as a target for new anti-neoplastic pharmacological strategies.
 
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Publishing Date
2011-07-27
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
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  • Bravo-Calderón, DM, et al. Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma. CANCER BIOMARK, 2012, vol. 10, p. 51-59.
  • Vilardi, BMR, et al. VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors [doi:10.1007/s13277-012-0521-1]. Tumor Biology [online], 2013, vol. 34, p. 139-143.
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  • Bravo-Calderón, DM, et al. Beta-2 adrenergic receptor expression in surgical margins of oral squamous cell carcinoma. In 16th International Congress on Oral Pathology and Medicine and 20th Brazilian Congress of Oral Medicine and Pathology 2012 (São Pedro-Brazil, 30th July 03rd August 2012), São Pedro, 2012. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology., 2012. Abstract.
  • Bravo-Calderón, DM, et al. Expressão de receptor beta-2 adrenérgico em carcinoma espinocelular de boca e sua associação com a evolução clínica tumoral. In XXVIII Reunião Anual da Sociedade Brasileira de Pesquisa Odontológica - Brazilian Division of the International Association for Dental Research., Águas de Lindóia, 2011. Brazilian Oral Research ., 2011. Resumo.
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  • Lauand, GA, et al. Receptor beta-2 adrenérgico: expressão no carcinoma espinocelular de boca e em suas margens cirúrgicas. In XX Simpósio Internacional de Iniciação Científica da Universidade de São Paulo (SIICUSP)., Ribeirão Preto, 2012. XX Simpósio Internacional de Iniciação Científica da Universidade de São Paulo.., 2012. Resumo.
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  • Vilardi, BMR, et al. VEGF expression in oral cancer by neurotransmitter-induced activation of beta adrenergic receptors. In 16th International Congress on Oral Pathology and Medicine and 20th Brazilian Congress of Oral Medicine and Pathology 2012 (São Pedro-Brazil, 30th July 03rd August 2012), São Pedro, 2012. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology., 2012. Abstract.
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  • Bravo-Calderón, DM, et al. Adenoid cystic carcinoma of the maxillary sinus with oral involvement. In 16th International Congress on Oral Pathology and Medicine and 20th Brazilian Congress of Oral Medicine and Pathology 2012 (São Pedro-Brazil, 30th July 03rd August 2012), São Pedro, 2012. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology., 2012. Abstract.
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  • Nicolielo, NFP, et al. Parafunctional habit lesion: a diagnostic challenge. In 16th International Congress on Oral Pathology and Medicine and 20th Brazilian Congress of Oral Medicine and Pathology 2012 (São Pedro-Brazil, 30th July 03rd August 2012), São Pedro, 2012. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology., 2012. Abstract.
  • Souza, TSN, et al. Atraso na erupção dentária causada por lesão hamartomatosa pericoronal. In XLI Jornada Odontológica 'Prof. Nicacio Garcia Hernandes', Lins, 2012. XLI Jornada Odontológica, XXV Jornada Acadêmica e XII Prata da Casa-Pós-graduação da Faculdade de Odontologia de Lins.., 2012. Resumo.
  • Souza, TSN, et al. Hiperplasia folicular pericoronária interferindo na erupção dentária. In XXV Congresso Odontológico de Bauru, Bauru, 2012. XXV Congresso Odontológico de Bauru - USP., 2012. Resumo.
  • TJIOE, Kellen Cristine, et al. Hybrid lesion with central giant cell lesion and fibro-Osseous components. In 16th International Congress on Oral Pathology and Medicine and 20th Brazilian Congress of Oral Medicine and Pathology 2012 (São Pedro-Brazil, 30th July 03rd August 2012), São Pedro, 2012. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology., 2012. Abstract.
  • Trevizo, BF, et al. Lesão de seio maxilar associada a dente tratado endodonticamente. In XXV Congresso Odontológico de Bauru, Bauru, 2012. XXV Congresso Odontológico de Bauru - USP., 2012. Resumo.
  • Trevizo, BF, et al. Nódulo gengival: fibroma odontogênico periférico. In XLI Jornada Odontológica 'Prof. Nicacio Garcia Hernandes', Lins, 2012. XLI Jornada Odontológica, XXV Jornada Acadêmica e XII Prata da Casa-Pós-graduação da Faculdade de Odontologia de Lins.., 2012. Resumo.
  • Weckwerth, G, et al. Carcinoma mucoepidermóide em lábio superior: uma rara ocorrência. In XLI Jornada Odontológica 'Prof. Nicacio Garcia Hernandes', Lins, 2012. XLI Jornada Odontológica, XXV Jornada Acadêmica e XII Prata da Casa-Pós-graduação da Faculdade de Odontologia de Lins.., 2012. Resumo.
  • Menção Honrosa no XX Simpósio Internacional de Iniciação Científica da USP com o trabalho "Receptor beta-2 adrenérgico: expressão no carcinoma espinocelular de boca e em suas margens cirúrgicas" - Pró-reitoria de Pesquisa da Universidade de São Paulo
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