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Master's Dissertation
DOI
https://doi.org/10.11606/D.25.2005.tde-17082005-111910
Document
Author
Full name
Renato Vieira de Moraes
Institute/School/College
Knowledge Area
Date of Defense
Published
Bauru, 2005
Supervisor
Committee
Consolaro, Alberto (President)
Landman, Gilles
Oliveira, Deilson Elgui de
Title in Portuguese
Carcinoma verrucoso de boca: análise das características clínica e microscópica, da expressão imuno-histoquímica e da hipermetilação do gene da E-caderina
Keywords in Portuguese
carcinoma
Abstract in Portuguese
O carcinoma verrucoso (CV), é considerado uma variante do carcinoma espinocelular (CEC) bem diferenciado, que se caracteriza por sua baixa agressividade e bom prognóstico e acomete principalmente a laringe e a boca. Um total de 1613 carcinomas espinocelulares primários de boca, cirurgicamente excisados entre 1980 e 2000, foram revisados dos arquivos dos Departamentos de Patologia e Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer A.C. Camargo. Dez CVs foram identificados e analisados quanto ao gênero, idade, raça, tabagismo, etilismo, localização do tumor primário, classificação pelo sistema TNM, tratamento, ocorrência de recidiva tumoral, metástases em linfonodos regionais, a distância e de segundo tumor primário. Analisaram-se também a expressão imuno-histoquímica e a hipermetilação da região promotora do gene da E-caderina, e os valores obtidos foram comparados com carcinomas espinocelulares bem diferenciados de boca sem (CEC-pN0) e com (CEC-pN+) comprometimento linfonodal. As probabilidades de sobrevidas, acumuladas nos períodos de cinco e dez anos para os grupos tumorais, foram calculadas pelo método de Kaplan-Meier. Os resultados demonstraram uma predileção dos CVs por pacientes do gênero masculino, tabagistas e etilistas, com idade superior a 67 anos, ocorrendo principalmente no lábio inferior. O tempo de história clínica foi maior que 16 meses e nenhum paciente com CV foi submetido à radioterapia e/ou quimioterapia pós-operatória. Microscopicamente as lesões eram bem características com intensa queratinização, padrão de invasão compressivo, pouca atipia e margens cirúrgicas livres. Uma maior expressão imunohistoquímica da E-caderina foi verificada nos carcinomas verrucosos quando comparados aos grupos de CEC-pN0 e CEC-pN+, sendo a diferença entre os grupos estatisticamente significativa (p= 0,016). O perfil de metilação do gene da E-caderina foi estatisticamente semelhante (p= 0,975) e superior a 50% nos três grupos de carcinomas de boca avaliados (CV, CEC-pN0 e CEC-pN+). A sobrevida global do grupo CV foi superior aos grupos de CECs bem diferenciados tanto em cinco quanto em dez anos (p= 0,012). Com base nestes resultados concluímos que o carcinoma verrucoso bucal apresenta um comportamento clínico e biológico relativo à expressão da E-caderina, mais favorável quando comparado carcinoma espinocelular bem diferenciado. A presença da hipermetilação do gene da E-caderina em neoplasias malignas com baixo potencial invasivo e metastático como o CV sugere que este evento epigenético ocorre precocemente nos mecanismos envolvidos na progressão tumoral.
Title in English
Oral verrucous carcinoma: clinicopathologic study, immunohistochemical expression and hypermethylation of E-cadherin gene analyses
Abstract in English
Verrucous carcinoma (VC), is considered a variant of well differentiated squamous cell carcinoma, that is characterized by its low aggressiveness and good prognostic and arises most frequently in the larynx and oral cavity. A total of 1613 cases of surgically excised primary oral squamous cell carcinoma from the files of Otohinolaryngology, Head and Neck Surgery, and Pathology Departments of the A.C. Camargo Cancer Hospital, from 1980 to 2000, were retrospectively reviewed. Ten cases of CVs were identified and analyzed as for the gender, age, race, tobacco and alcohol abuse, localization, stage by the TNM-UICC, treatment, lymph nodes involvement, local and cervical recurrences, distant metastasis and second primary tumors. In addition, we investigated the immunohistochemical expression of the Ecadherin and the promoter region hypermethylation of the E-cadherin gene of VCs comparing with oral well differentiated squamous cell carcinoma without (SCC-pN0) and with (SCCpN+) lymph nodes involvement. The 5 and 10-year survival rates were calculated by Kaplan- Meyer method. The results demonstrated a predilection of VCs for patients of the masculine gender, with positive tobacco and alcohol history, with age older than 67 years and arise predominantly in the inferior lip. The clinical history was longer than 16 months and no patient with VC was submitted the radiotherapy and/or chemotherapy postoperative. The histopathologic analysis showed a heavily keratinized lesion with compressive invasion pattern, little atypia and free surgical margins. In comparison with SCC-pN0 and SCC-pN+, verrucous carcinoma showed a higher immunohistochemical expression of the E-cadherin score (p= 0,016). More than 50% of the tumors showed the hypermethylation of the Ecadherin gene and no statistically significant differences (p= 0,975) were found among VC, SCC-pN0 and SCC-pN+ groups. Verrucous carcinoma of the oral cavity had significantly better 5-year and 10-year overall survival rates than the well differentiated squamous cell carcinomas (p= 0,012). These results permit to conclude that the oral verrucous carcinoma presents more favorable clinical and biological behavior related to the immunohistochemical expression of the E-cadherin when compared with well differentiated squamous cell carcinoma. The presence of the hypermethylation of the E-cadherin gene in the malignant tumors with lower potential invasive and metastatic, such as VC, suggests that this epigenetic event happens early in the mechanisms involved in the tumoral progression.
 
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Publishing Date
2005-08-22
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • MORAES, Renato Vieira de, et al. Abnormalities of E-cadherin expression resulting from CpG methylation promoter occur in metastatic and non-metastatic oral squamous cell carinomas. Journal of Oral Pathology and Medicine, 2006, vol. 35, nº 07, p. 440-441. Abstract.
  • MORAES, Renato Vieira de, et al. E-cadherin abnormalities resulting from CpG methylation promoter in metastatic and non-metastatic oral cancer. Braz Oral Res, 2005, vol. 19, p. 19-19. Abstract.
  • MORAES, Renato Vieira, et al. E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancer [doi:10.1002/hed.20666]. Head & Neck [online], 2008, vol. 30, p. 85-92.
  • Oliveira, Denise Tostes, et al. Oral verrucous carcinoma: a retrospective study in São Paulo Region, Brazil [doi:10.1007/s00784-006-0050-7]. Clinical Oral Investigations [online], 2006, vol. 10, p. 205-209.
  • MORAES, Renato Vieira de, et al. Abnormalities of E-cadherin expression resulting from CpG methylation promoter occur in metastatic and non-metastatic oral squamous cell carcinomas. In 13th International Congress on Oral Pathology and Medicine, Bisbrane, 2006. 13th International Congress on Oral Pathology and Medicine., 2006. Abstract.
  • MORAES, Renato Vieira de, et al. E-cadherin abnormalities resulting from CpG methylation promoter in metastatic and non-metastatic oral cancer. In XXII Reunião Anual da Sociedade Brasileira de Pesquisa Odontológica., Águas de Lindóia, 2005. Proceedings of the XXII Annual SBPqO Meeting., 2005. Abstract.
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