No município de São Paulo, em 1970 foram relatados 169 casos novos de câncer de laringe, com uma taxa de incidência ajustada por idade pela população mundial de 25,5/100.000 (30-74 anos) e 299 casos em 1985, elevando a taxa para 37,6 (ambos nosexo masculino). O Tabagismo e o consumo de álcool são os fatores de risco mais bem estabelecidos para o câncer de laringe. Com relação aos fatores ocupacionais, o único carcinógeno estabelecido é a exposição à névoa de ácidos inorgânicosfortes. É proposto um estudo caso-controle de base hospitalar, para investigar e quantificar o papel da exposição ocupacional no desenvolvimento do câncer de laringe e é discutida uma nova proposta de avaliação de exposição que visa melhorar avalidade interna desse tipo de estudo / Laryngeal cancer comprises 3,1% of the new cases of cancer in men in the world, representing the tenth most common malign neoplasm for males. In São Paulo City, 169 new cases of laryngeal cancer were reported in 1970, representing 25,5/100.000 and 299 cases in 1985, increasing the rate to 37,6/100.000 (both for males, age standardized truncated rate, 30-74 years). The best established risk factors for laryngeal cancer are tobacco and alcohol. In respect to occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline and diesel engine emissions, dusts, among other factors are reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted, in seven hospitals in São Paulo, to investigate occupational risk factors for laryngeal cancer. The study included 122 laryngeal cancers and 187 controls, selected by frequency matching on sex and age. Detailed information on smoking, alcohol consumption, and occupational history was collected. Occupational hygienists assessed the exposure to 49 agents. Odds Ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression, and were adjusted for sex, age, smoking and alcohol. Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR 1,83, 95% CI 1,00 - 3,36), soot (from coal, coke, fuel oil, wood) (OR 1,78, 95% CI 1,03 - 3,03), fumes (OR 2,55, CI 95% 1,14 - 5,67) and to live animals (OR 1,80, 95% CI 1,02 - 3,19). This study showed that occupational exposures to: respirable free crystalline silica, soot (from coal, coke, fuel oil, wood), fumes and live animals are risk factors for laryngeal cancer.

Orientador: Carlos Takahiro Chone / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T13:57:24Z (GMT). No. of bitstreams: 1 Moraes_JulianaLopesde_M.pdf: 943040 bytes, checksum: 4d94adb829d86ae614ad5e737c31b7af (MD5) Previous issue date: 2014 / Resumo: Objetivo: Comparar a qualidade de vida do paciente tratado cirurgicamente por câncer avançado de laringe com aquele que foi submetido a quimioradioterapia exclusivos. Método: Revisão sistemática que utilizou, para a seleção dos artigos, 06 bases de dados (PubMed, MedLine, Embase, Web of Science, Cochrane Library e Lilacs) e as palavras-chave "head and neck cancer"; "advanced laryngeal cancer"; "laryngeal neoplasm"; larynx cancer"; "quality of life"; "outcomes/functional results";"total laringectomy"; "chemoradiotherapy". Os critérios de inclusão foram estudos específicos de câncer avançado de laringe, com comparação de modalidades de tratamento e avaliação da qualidade de vida. Resultados: Foram encontrados 321 artigos. Nove artigos preencheram todos os critérios de inclusão e desses, apenas três possuíam desenho metodológico e instrumento de mensuração de qualidade de vida comparáveis entre si e foram submetidos à metanálise . Os resultados evidenciaram que 90% dos estudos são retrospectivos e não randomizados. O tempo pós-tratamento em que os questionários de qualidade de vida foram aplicados mostrou grande variabilidade (3 meses a 11 anos). Conclusão: A meta-análise dos três estudos comparativos mostraram uma melhor qualidade de vida após o tratamento para indivíduos tratados com quimioradioterapia exlcusiva. No entanto, devido a existência de poucos estudos com dados relevantes na literatura, é necessário realizar pesquisas futuras com as seguintes características: (a) estudos prospectivos e randomizados, (b) multicêntrico, com maior número de indivíduos, e (c) enfatizando o funcional sequelas que ambos os tratamentos acarretam / Abstract: Objective: To compare studies of quality of life in patients undergoing chemoradiotherapy or surgery for advanced laryngeal cancer. Method: Articles were selected for a systematic review by searching six databases (PubMed, Medline, Embase, Web of Science, Cochrane Library and Lilacs) for keywords "head and neck cancer," "advanced laryngeal cancer," "laryngeal neoplasm," "larynx cancer," "quality of life," "outcomes and functional results," "total laryngectomy" and "chemoradiotherapy." The included studies must related to advanced larynx cancer, comparisons of treatment modalities and assessment of patient quality of life in validated scales, well defined inclusion and exclusion criteria. Articles with poor methodological evaluation and duplicated results were excluded. Results: It was found 321 articles. Nine articles fitted to all inclusion criteria and of these, only three observed comparable methodological designs and standardized instruments for measuring quality of life and therefore subjected to meta-analysis. Our analysis observed that 90% of the studies were retrospective and nonrandomized. The time point post-treatment at which the quality of life questionnaires were assessed varied widely (3 months to 11 years). Conclusion: The meta-analysis of three comparable studies showed improved quality of life after treatment for subjects treated with chemoradiation alone. However, because of few studies with relevant data in literature, it is necessary to conduct future research with the following study characteristics: (a) prospective and randomized; (b) multicentric, with larger numbers of subjects; and (c) emphasizing the functional sequelae that both treatments entail / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas

Abstract Automated quantitative computer-assisted morphometric analysis of immunohistochemical expression of markers of neoplastic development and progression in experimentally induced and in human neoplasms showed very high sensitivity and reproducibility, allowing analysis of large numbers of cell and tissue components. Totals of 26 million pixels, 25,000 cells and 1500 vessels were examined, with a sensitivity exceeding 99% and reproducibility exceeding 99%. The total expression of proliferating cell nuclear antigen (PCNA) and p53 increased consistently during 7H-dibenz[c, g] carbazole (DBC)-induced formation of dysplasias and squamous cell carcinomas (SCC:s) in hamster lung. In dysplasia, nuclear size and PCNA staining intensity increased; in SCC:s nuclear size decreased. In a retrospective study on archival material of human laryngeal squamous cell carcinomas, the occurrence and location of PCNA-positive cells were specifically related to the degree of differentiation. In SCC:s nuclear size decreased, while shape alterations and PCNA staining intensity increased in relation to degree of malignancy. In DBC-induced respiratory carcinogenesis increased collagen matrix synthesis occurred prior to neoplasm development. Among squamous cell carcinomas, in well-differentiated tumors, collagen deposition increased, as did fiber size, in moderately differentiated tumors collagen synthesis and the deposition of new collagen decreased. The increase in transforming growth factor beta expression in differentiated cells and in the matrix was isoform-specific. Increased angiogenesis in laryngeal tumor development occurred in preneoplastic states and in SCC: s, inversely related to the degree of differentiation. In well-differentiated neoplasms the vessels were lying in the direction of the BM, in moderately differentiated neoplasms vessels were lying in the direction of tumor invasion and in poorly differentiated neoplasms irregular, partly abnormal vessels intermixed with tumor cells. Small regular vessels predominated in benign conditions and large, irregular vessels in malignant conditions. Experimental models provided the advantage of examining homogenous, well-characterized neoplasm progression without interfering with the process. Morphometric methods provided detailed information on large numbers of cells, useful for studies of tumor behavior and with potential clinical applications.

Introdução: A comissura anterior constitui-se em área de infiltração do câncer glótico, mesmo em estádio precoce. Objetivo: Avaliar o acometimento por tumor da cartilagem da comissura anterior em espécimes de laringectomia frontolateral. Métodos: Foram incluídos 48 pacientes submetidos à laringectomia frontolateral por carcinoma espinocelular T1b/T2. Aspectos epidemiológicos, clínicos e análise morfológica histopatológica foram avaliados. Resultados: Quarenta e dois pacientes (87,5%) tinham lesões T1b e seis (12,5%), T2. Trinta e quatro casos (70,8%) apresentaram tecido sadio entre o tumor e a cartilagem tireoidea, 10 casos (20,8%) tinham tumor contíguo à cartilagem e, em quatro casos (8,3%), houve invasão da cartilagem. Não houve maior risco de desfecho adverso nos grupos com infiltração ou tumor adjacente à cartilagem. Grau de diferenciação, índice mitótico, irregularidade nuclear, presença de nucléolo e necrose tumoral não tiveram relação com invasão da cartilagem. Conclusão: A infiltração da cartilagem tireoidea ocorreu em 8,3% dos tumores e não mudou o desfecho em pacientes submetidos à laringectomia fronto-lateral. As características morfológicas não apresentaram significado estatístico / Introduction: The anterior commissure is an area of glottic cancer infiltration, even in early stages. Objective: To evaluate the involvement of cartilage by the tumor of the anterior commissure in surgical specimens of frontolateral laryngectomy. Methods: 48 patients who had undergone frontolateral laryngectomy for T1b/T2 squamous cell carcinoma were included. Epidemiological and clinical aspects as well as morphological histopathological analysis were evaluated. Results: 42 patients (87,5%) had T1b lesions and 6 (12,5%) had T2. Thirty-four cases (70,8%) showed healthy tissue between the tumor and thyroid cartilage, 10 cases (20,8%) had a tumor contiguous with cartilage; and in 4 cases (8,3%) there was cartilage invasion. There was no major risk of adverse closure in the groups with the infiltration or tumor adjacent to cartilage. Grade of cellular differentiation, mitotic index, nuclear irregularity, the presence of nucleolus and tumoral necrosis were not related to cartilage invasion. Conclusion: the infiltration of thyroid cartilage occurred in 8,3% of tumors and did not change the outcome in patients submitted to partial frontolateral laryngectomy. The morphological characteristics did not show any statistical significance

Introdução: A comissura anterior constitui-se em área de infiltração do câncer glótico, mesmo em estádio precoce. Objetivo: Avaliar o acometimento por tumor da cartilagem da comissura anterior em espécimes de laringectomia frontolateral. Métodos: Foram incluídos 48 pacientes submetidos à laringectomia frontolateral por carcinoma espinocelular T1b/T2. Aspectos epidemiológicos, clínicos e análise morfológica histopatológica foram avaliados. Resultados: Quarenta e dois pacientes (87,5%) tinham lesões T1b e seis (12,5%), T2. Trinta e quatro casos (70,8%) apresentaram tecido sadio entre o tumor e a cartilagem tireoidea, 10 casos (20,8%) tinham tumor contíguo à cartilagem e, em quatro casos (8,3%), houve invasão da cartilagem. Não houve maior risco de desfecho adverso nos grupos com infiltração ou tumor adjacente à cartilagem. Grau de diferenciação, índice mitótico, irregularidade nuclear, presença de nucléolo e necrose tumoral não tiveram relação com invasão da cartilagem. Conclusão: A infiltração da cartilagem tireoidea ocorreu em 8,3% dos tumores e não mudou o desfecho em pacientes submetidos à laringectomia fronto-lateral. As características morfológicas não apresentaram significado estatístico / Introduction: The anterior commissure is an area of glottic cancer infiltration, even in early stages. Objective: To evaluate the involvement of cartilage by the tumor of the anterior commissure in surgical specimens of frontolateral laryngectomy. Methods: 48 patients who had undergone frontolateral laryngectomy for T1b/T2 squamous cell carcinoma were included. Epidemiological and clinical aspects as well as morphological histopathological analysis were evaluated. Results: 42 patients (87,5%) had T1b lesions and 6 (12,5%) had T2. Thirty-four cases (70,8%) showed healthy tissue between the tumor and thyroid cartilage, 10 cases (20,8%) had a tumor contiguous with cartilage; and in 4 cases (8,3%) there was cartilage invasion. There was no major risk of adverse closure in the groups with the infiltration or tumor adjacent to cartilage. Grade of cellular differentiation, mitotic index, nuclear irregularity, the presence of nucleolus and tumoral necrosis were not related to cartilage invasion. Conclusion: the infiltration of thyroid cartilage occurred in 8,3% of tumors and did not change the outcome in patients submitted to partial frontolateral laryngectomy. The morphological characteristics did not show any statistical significance

INTRODUÇÃO: Alterações genéticas múltiplas são comuns durante a carcinogênese e, nesse panorama, o gene supressor tumoral TP53 é um dos mais associados à transformação maligna. Recentemente, dois genes similares ao TP53, foram identificados, o TP73 e o TP63. O TP63 situa-se no cromossomo 3q e tem papel comprovado no desenvolvimento epidérmico, sendo detectado em vários tecidos humanos. Inúmeros trabalhos relacionaram a expressão da proteína p63 com carcinomas do trato aerodigestivo superior. OBJETIVOS: O presente estudo objetivou avaliar a expressão Imunoistoquímica da proteína p63 e seu valor prognóstico nos carcinomas epidermóides da laringe. CASUÍSTICA E MÉTODOS: Foram estudados retrospectivamente 127 pacientes submetidos a laringectomia total no Instituto Nacional de Câncer, Rio de Janeiro, entre 1998 e 2000. Houve 111 doentes masculinos e 16 femininos, 69 brancos e 58 não-brancos, com idade entre 36 a 93 anos, média de 59 e mediana de 58 anos. Dezenove tumores eram glóticos, 16 supraglóticos e 92 acometiam mais de um local, correspondendo a 15%, 13% e 72% respectivamente. Quanto ao estadiamento clínico, dois casos eram do estádio I (1,6%), 21 do II (16,5%), 82 do III (64,6%) e 22 do IV (17,3%). Noventa e seis pacientes (75,6%) receberam radioterapia complementar. A técnica imunoistoquímica, com anticorpos monoclonais do clone 4A4, foi utilizada para estudar a expressão da p63. O percentual de células imunocoradas positivamente foi estimado conforme os seguintes escores: 0: ausência de imunocoloração; 1: imunocoloração em < 30% das células neoplásicas; 2: imunocoloração em > 30% e < 70% das células neoplásicas; e 3: imunocoloração em > 70% das células neoplásicas. Foram observados 62 casos do escore 3 (+++), 60 do escore 2 (++), 4 do 1 (+) e 1 caso sem expressão (0), correspondendo respectivamente a 48,8%, 47,2%, 3,1% e 0,8% da amostra. Através de análises uni e multivariadas, a imunoexpressão da proteína p63 e os outros fatores de provável impacto prognóstico foram avaliados quanto ao grau de associação aos eventos recidiva e óbito. RESULTADOS: A análise multivariada identificou a imunoexpressão da proteína p63 e o envolvimento da hipofaringe como preditivas para ocorrência de recidiva e óbito pelo carcinoma. A sobrevida global foi de 73,9% em 24 meses e de 59,5% em 60 meses. A sobrevida livre de recorrência foi de 77,2% e 75,1%, e a sobrevida relacionada ao óbito pelo carcinoma foi de 79% e 67% em 24 e 60 meses respectivamente. CONCLUSÕES: Apenas a recidiva associou-se estatisticamente à expressão da proteína p63. A p63 se mostrou altamente expressa nos carcinomas epidermóides de laringe e, apesar dos poucos casos com expressão reduzida, a hipoexpressão da p63 foi preditiva de um pior prognóstico nesses doentes. / INTRODUCTION: Multiple genetic changes are common during carcinogenesis and, in this scene, the gene TP53 is one of the most associated with malignant transformation. Recently, two related genes to the TP53, were identified, the TP73 and TP63. The TP63 stands on the chromosome 3q and has a proven role in the epidermal development, being detected in several human tissues. Many work linked the expression of p63 protein with carcinomas of the upper aero-digestive tract. OBJECTIVE: The objective of this study was to evaluate the immunohistochemical expression of p63 protein and its prognostic value in squamous cell carcinomas of the larynx. CASUISTRY AND METHODS: The p63 expression has been examined in 127 patients who were submitted to total laryngectomy, with or without adjuvant radiotherapy, in the Brazilian National Cancer Institute, between 1998 and 2000. There were 111 male patients and 16 female, 69 white and 58 non-white, aged between 36 to 93 years, average 59 and median of 58 years. Nineteen tumors were glottic, 16 supraglottic and 92 affected more than one place, corresponding to 15%, 13% and 72% respectively. As to the clinical staging, two cases were stage I (1.6%), 21 of the II (16.5%), 82 of the III (64.6%) and 22 of the IV (17.3%). Ninety-six patients (75.6%) received complementary radiotherapy. The immunohistochemical technique with the use of monoclonal antibodies of clone 4A4, has been used to study the expression of p63. The percentage of positive cells was estimated as the following scores: 0: no immunostaining; 1: immunostaining in <30% of neoplastics cells; 2: immunostaining in >30% and <70% of neoplastics cells; And 3: immunostaining in >70% of neoplastics cells. Sixty two cases were observed in score three, 60 in score two 4 in score one (+) and 1 case without expression (0), corresponding respectively to 48.8%, 47.2%, 3.1% and 0.8% of the sample. Through uni and multivariate analysis, the immunoexpression of p63 protein and the other factors likely to impact prognosis were evaluated on the degree of association to recurrence and death. RESULTS: The multivariate analysis identified the immunoexpression of protein p63 and the involvement of the hypopharynx as statistically significant for the risk of recurrence and death by cancer. The overall survival was 73.9% in 24 months and 59.5% at 60 months. CONCLUSIONS: The disease-free survival was 77.2% and 75.1%, and the disease-specific survival was 79% and 67% at 24 and 60 months respectively. The p63 protein was highly expressed in squamous cell laryngeal carcinomas. In spite of few cases with reduced expression, p63 protein underexpression was statistically associated to the recurrence and may have a negative impact upon prognosis.

Lo, Chun Shan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 71-80). / Abstracts in English and Chinese. / Abstract --- p.i / Chinese abstract --- p.iii / Acknowledgements --- p.iv / List of figures --- p.vi / Abbreviations --- p.vii / Contents --- p.viii / Chapter Chapter One --- General Introduction --- p.Page / Chapter 1.1 --- Background --- p.1 / Chapter 1.2 --- Human papillomavirus infection at the larynx --- p.2 / Chapter 1.2.1 --- Biology of human papillomavirus --- p.4 / Chapter 1.2.2 --- HPV E6 protein --- p.5 / Chapter 1.2.3 --- HPV E7 protein --- p.7 / Chapter 1.3 --- Apoptosis --- p.9 / Chapter 1.3.1 --- Apoptosis signaling pathways --- p.11 / Chapter 1.4 --- Transcription factor: Nuclear factor -kB --- p.14 / Chapter 1.4.1 --- Overview of the NF-kB signaling pathway --- p.14 / Chapter 1.4.2 --- Regulation of NF-kB signaling --- p.16 / Chapter 1.4.3 --- Roles of NF-kB in cancers --- p.19 / Chapter 1.5 --- Pteris semipinnata L extract: ent-11 -hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) --- p.21 / Chapter 1.6 --- Objectives --- p.22 / Chapter Chapter Two --- Materials and Methods / Chapter 2.1 --- Cell culture --- p.24 / Chapter 2.2 --- Cell proliferation analysis --- p.24 / Chapter 2.3 --- Western Blotting --- p.26 / Chapter 2.3.1 --- Total protein extraction --- p.26 / Chapter 2.3.2 --- Nuclear and cytoplasmic protein extraction --- p.26 / Chapter 2.3.3 --- Quantification of protein concentration --- p.27 / Chapter 2.3.4 --- Sodium dodecyl sulfate - polyacylamide gel electrophoresis (SDS-PAGE) and protein transfer --- p.28 / Chapter 2.3.5 --- Immunoblotting --- p.29 / Chapter 2.4 --- NF-kB Luciferase Assay --- p.29 / Chapter 2.5 --- Annexin V apoptosis assay --- p.31 / Chapter 2.6 --- mRNA expression analyses --- p.33 / Chapter 2.6.1 --- RNA extraction --- p.33 / Chapter 2.6.2 --- Reverse Transcription --- p.33 / Chapter 2.6.3 --- Polymerase Chain Reaction --- p.34 / Chapter 2.7 --- Antibodies --- p.35 / Chapter Chapter Three --- Results / Chapter 3.1 --- "Anti-proliferation effect of 5F on laryngeal cancer cells UMSCC11A, UMSCC12 and HEp-2 cells" --- p.36 / Chapter 3.2 --- Suppression by 5F in HEp-2 of mRNA and protein expression levels in HPV18 E7 while the expression level of HPV18 E6 was not altered --- p.38 / Chapter 3.3 --- Quantification of 5F-induced apoptosis in laryngeal cancer cells by Annexin V assay --- p.40 / Chapter 3.4 --- Morphological changes in laryngeal cancer cells induced by 5F --- p.41 / Chapter 3.5 --- "Cleavage of poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 induced by 5F in UMSCC11 A, UMSCC12 and HEp-2 cell lines" --- p.47 / Chapter 3.6 --- "Down-regulation of TNF-α-induced NF-kB subunit p65 and p50 nuclear translocations in UMSCC11 A, UMSCC12 and HEp-2 by 5F" --- p.47 / Chapter 3.7 --- Dose-dependent inhibition of 5F on NF-kB transcriptional activity measured by luciferase assay --- p.53 / Chapter 3.8 --- Partial inhibition of TNF-α induced kBα degradation by 5F in UMSCC11A but not in UMSCC12 and HEp-2 --- p.56 / Chapter 3.9 --- Cell proliferation inhibition and apoptosis induction by Bay (11-7082) in laryngeal cancer cells --- p.56 / Chapter 3.10 --- Differential basal nuclear translocation of p65 and p50 in laryngeal cancer cell lines --- p.57 / Chapter 3.11 --- 5F regulated NF-kB target gene expression --- p.58 / Chapter Chapter Four --- Discussions --- p.64 / Reference --- p.71 / Appendix / Appendix 1 Map of pLuc- NF-kB plasmid --- p.81

INTRODUÇÃO: Alterações genéticas múltiplas são comuns durante a carcinogênese e, nesse panorama, o gene supressor tumoral TP53 é um dos mais associados à transformação maligna. Recentemente, dois genes similares ao TP53, foram identificados, o TP73 e o TP63. O TP63 situa-se no cromossomo 3q e tem papel comprovado no desenvolvimento epidérmico, sendo detectado em vários tecidos humanos. Inúmeros trabalhos relacionaram a expressão da proteína p63 com carcinomas do trato aerodigestivo superior. OBJETIVOS: O presente estudo objetivou avaliar a expressão Imunoistoquímica da proteína p63 e seu valor prognóstico nos carcinomas epidermóides da laringe. CASUÍSTICA E MÉTODOS: Foram estudados retrospectivamente 127 pacientes submetidos a laringectomia total no Instituto Nacional de Câncer, Rio de Janeiro, entre 1998 e 2000. Houve 111 doentes masculinos e 16 femininos, 69 brancos e 58 não-brancos, com idade entre 36 a 93 anos, média de 59 e mediana de 58 anos. Dezenove tumores eram glóticos, 16 supraglóticos e 92 acometiam mais de um local, correspondendo a 15%, 13% e 72% respectivamente. Quanto ao estadiamento clínico, dois casos eram do estádio I (1,6%), 21 do II (16,5%), 82 do III (64,6%) e 22 do IV (17,3%). Noventa e seis pacientes (75,6%) receberam radioterapia complementar. A técnica imunoistoquímica, com anticorpos monoclonais do clone 4A4, foi utilizada para estudar a expressão da p63. O percentual de células imunocoradas positivamente foi estimado conforme os seguintes escores: 0: ausência de imunocoloração; 1: imunocoloração em < 30% das células neoplásicas; 2: imunocoloração em > 30% e < 70% das células neoplásicas; e 3: imunocoloração em > 70% das células neoplásicas. Foram observados 62 casos do escore 3 (+++), 60 do escore 2 (++), 4 do 1 (+) e 1 caso sem expressão (0), correspondendo respectivamente a 48,8%, 47,2%, 3,1% e 0,8% da amostra. Através de análises uni e multivariadas, a imunoexpressão da proteína p63 e os outros fatores de provável impacto prognóstico foram avaliados quanto ao grau de associação aos eventos recidiva e óbito. RESULTADOS: A análise multivariada identificou a imunoexpressão da proteína p63 e o envolvimento da hipofaringe como preditivas para ocorrência de recidiva e óbito pelo carcinoma. A sobrevida global foi de 73,9% em 24 meses e de 59,5% em 60 meses. A sobrevida livre de recorrência foi de 77,2% e 75,1%, e a sobrevida relacionada ao óbito pelo carcinoma foi de 79% e 67% em 24 e 60 meses respectivamente. CONCLUSÕES: Apenas a recidiva associou-se estatisticamente à expressão da proteína p63. A p63 se mostrou altamente expressa nos carcinomas epidermóides de laringe e, apesar dos poucos casos com expressão reduzida, a hipoexpressão da p63 foi preditiva de um pior prognóstico nesses doentes. / INTRODUCTION: Multiple genetic changes are common during carcinogenesis and, in this scene, the gene TP53 is one of the most associated with malignant transformation. Recently, two related genes to the TP53, were identified, the TP73 and TP63. The TP63 stands on the chromosome 3q and has a proven role in the epidermal development, being detected in several human tissues. Many work linked the expression of p63 protein with carcinomas of the upper aero-digestive tract. OBJECTIVE: The objective of this study was to evaluate the immunohistochemical expression of p63 protein and its prognostic value in squamous cell carcinomas of the larynx. CASUISTRY AND METHODS: The p63 expression has been examined in 127 patients who were submitted to total laryngectomy, with or without adjuvant radiotherapy, in the Brazilian National Cancer Institute, between 1998 and 2000. There were 111 male patients and 16 female, 69 white and 58 non-white, aged between 36 to 93 years, average 59 and median of 58 years. Nineteen tumors were glottic, 16 supraglottic and 92 affected more than one place, corresponding to 15%, 13% and 72% respectively. As to the clinical staging, two cases were stage I (1.6%), 21 of the II (16.5%), 82 of the III (64.6%) and 22 of the IV (17.3%). Ninety-six patients (75.6%) received complementary radiotherapy. The immunohistochemical technique with the use of monoclonal antibodies of clone 4A4, has been used to study the expression of p63. The percentage of positive cells was estimated as the following scores: 0: no immunostaining; 1: immunostaining in <30% of neoplastics cells; 2: immunostaining in >30% and <70% of neoplastics cells; And 3: immunostaining in >70% of neoplastics cells. Sixty two cases were observed in score three, 60 in score two 4 in score one (+) and 1 case without expression (0), corresponding respectively to 48.8%, 47.2%, 3.1% and 0.8% of the sample. Through uni and multivariate analysis, the immunoexpression of p63 protein and the other factors likely to impact prognosis were evaluated on the degree of association to recurrence and death. RESULTS: The multivariate analysis identified the immunoexpression of protein p63 and the involvement of the hypopharynx as statistically significant for the risk of recurrence and death by cancer. The overall survival was 73.9% in 24 months and 59.5% at 60 months. CONCLUSIONS: The disease-free survival was 77.2% and 75.1%, and the disease-specific survival was 79% and 67% at 24 and 60 months respectively. The p63 protein was highly expressed in squamous cell laryngeal carcinomas. In spite of few cases with reduced expression, p63 protein underexpression was statistically associated to the recurrence and may have a negative impact upon prognosis.

Foi realizado estudo caso-controle de base hospitalar, envolvendo pacientes diagnosticados com câncer de cabeça e pescoço e que participaram do \"Estudo Multicêntrico Latino-americano de Fatores Ambientais, Vírus e Câncer da Cavidade Oral e Laringe\" do projeto \"Genoma Clínico do Câncer\". Foram incluídos pacientes atendidos no Hospital Heliópolis, no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Instituto do Câncer Arnaldo Vieira de Carvalho entre novembro de 1998 e dezembro de 2005. Consideraram-se casos os pacientes com diagnóstico histologicamente confirmado de câncer de boca, faringe ou laringe e controles pessoas atendidas nos mesmos hospitais por outros motivos que não neoplasia maligna e doenças associadas com os fatores de risco do câncer de cabeça e pescoço. A análise empregou regressão logística não-condicional baseada em modelo hierárquico de determinação. No nível mais distal foram incluídas as variáveis demográficas (sexo, cor de pele e idade), seguidas pela escolaridade (série mais elevada que a pessoa cursou) e ocupação (exercida por mais tempo). No nível mais proximal, foram considerados o consumo de tabaco e de álcool. Também foi investigado se a associação de instrução e ocupação com câncer de cabeça e pescoço se mediava apenas por padrões diferenciais de consumo de álcool e tabaco entre os estratos sociais, ou se havia variação residual que excedia esses dois fatores. Todas as análises conduzidas para câncer de cabeça e pescoço foram replicadas de modo específico para as localizações topográficas da boca, faringe e laringe em separado. O estudo foi aprovado pelo Comitê de Ética da Faculdade de Odontologia da Universidade de São Paulo sob parecer no. 68/07 e os procedimentos estatísticos foram realizados no programa Stata 9. A amostra foi composta por 1017 casos e 951 controles. A análise hierárquica identificou maior chance de câncer de cabeça e pescoço entre os homens (OR=2,01; IC95% 1,57-2,59), pessoas entre 48 e 55 anos (OR=1,82; IC95% 1,42-2,33), pessoas sem estudo ou apenas alfabetizados (2,48; IC95% 1,73-3,52), entre pessoas com primeiro grau completo ou incompleto (1,31; IC95% 1,05-1,63) e entre as pessoas que exerceram durante mais tempo profissão manual (1,38; IC95% 1,10-1,74). Além disso, fumantes e consumidores de bebidas alcoólicas apresentaram maior razão de chances em relação àqueles que nunca consumiram os produtos. No modelo não hierárquico, mesmo após o ajuste por tabagismo e ingestão de álcool, maior chance foi verificada para o grupo de menor escolaridade em todas as localizações topográficas (exceto para os tumores de boca), e para pessoas com ocupações manuais (exceto para os tumores de boca e faringe). A identificação desse efeito residual indica haver fatores adicionais, além da exposição ao álcool e tabaco, operando na distribuição desigual do câncer de cabeça e pescoço entre os estratos sociais. / This is a hospital-based case-control study involving patients diagnosed with head and neck cancer. Such patients have participated in the \"Latin American Multicentric Study from Environmental Factors, Virus and Oral Cavity and Larynx Cancer\", and in the \"Clinical Genome of Cancer Project\", from November 1998 to December 2005, and were attended at the Hospital Heliópolis, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer Arnaldo Vieira de Carvalho. The case group comprised patients histologically diagnosed with mouth, pharynx or larynx cancer; the control group comprised patients treated at the same hospitals for other diseases than malignant neoplasms or conditions related to head and neck cancer risk factors. Data analysis used non-conditional logistic regression based on a hierarchical model of determination. At the most distal level, demographic variables were included (e.g. sex, skin color and age), followed by education level (e.g. highest grade or degree completed) and occupation (i.e. the one performed the longest period). Alcohol and tobacco consumption were included at the most proximal level. The investigation also assessed whether the association between education level and occupation with mouth and neck cancer was only mediated by differential patterns of alcohol and tobacco consumption among social strata, or there was residual variation that exceeded those two factors. All analyses for mouth and neck cancer were specifically replicated for each topographic location (mouth, pharynx and larynx). The study was approved by the University of Sao Paulo School of Dentistry\'s Ethics Committee, report number 68/07, and statistical analyses used the Stata 9 program. The sample was composed of 1017 cases and 951 controls. Hierarchical analysis identified a greater chance of head and neck cancer for men (OR=2,01; CI95% 1,57-2,59), patients aged 48 to 55 years old (OR=1,82; CI95% 1,42-2,33), uneducated or semi-literate patients (2,48; CI95% 1,73-3,52), subjects with elementary education (8 years) (1,31; IC95% 1,05-1,63) and those performing manual occupations (1,38; CI95% 1,10-1,74). In addition, tobacco smokers and alcohol users presented a higher odds than those non-exposed to these conditions. In the non-hierarchical model, even after the adjustment for tobacco and alcohol use, a higher odds was identified for the less-schooled strata in every topographic location (except for mouth tumors), and for subjects with manual labor occupations (except for mouth and pharynx tumors). Identification of such residual effect indicates that there are other factors than alcohol and tobacco consumption, which mediate the uneven distribution of head and neck cancer across the socioeconomic strata.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2017-02-17T12:40:05Z No. of bitstreams: 1 isabelcristinafigueiredo_dissert.pdf: 1024619 bytes, checksum: 795ba91ed5f42f76352cb849e415b1af (MD5) / Made available in DSpace on 2017-02-17T12:40:06Z (GMT). No. of bitstreams: 1 isabelcristinafigueiredo_dissert.pdf: 1024619 bytes, checksum: 795ba91ed5f42f76352cb849e415b1af (MD5) Previous issue date: 2015-10-01 / Introduction: Worldwidely head and neck cancer is the sixth as the most frequent cancer; 40% occurs in the oral cavity; 25% in the larynx; 15% in the pharynx and 20% in other anatomical sites. Objectives:. To analyze the association of cases of head and neck cancer and the outcome of speech rehabilitation of people with cancer of the larynx. Materials and Methods: Cross-sectional, quantitative study through survey data from medical records of patients with head and neck cancer, treated from 1989 to 2015, at Hospital de Base, São José do Rio Preto / SP, from three dimensions: socio-demographic, clinical and speech rehabilitation. The first study analyzed the correlation for cancers and variables (gender, place of origin, age and education). The second study was analyzed by univariate and multivariate techniques. Qualitative data were associated by applying the Chi-Square test. The multivariate approach through the multiple correspondence analysis enabling relations between the most important variables in the study. Results: In the first study: 52.7% were male with median age of 56 years; higher prevalence from 41 years (82.2%); 64.3% were from other cities in the state of São Paulo. Tumor predominantly affecting structures of the head and neck; presented in 53.2% of the cases. In the second study, according to the speech rehabilitation, 75.49% had alterations in the neuro-vegetative system, developed speech and voice (64.22%); of these, 22.55% esophageal voice; 21.57%) development of written communication and gestural; schooling was significantly associated with the outcome of Speech Therapy (P <0.001). The gestural communication was more frequent in patients with no schooling, improvement of dysphagia in patients with primary education, improvement of dysphagia / dysphonia and voice with electrolarynx in patients with secondary education. Most of patients with T2 and T4 tumor stage improved dysphagia and dysphonia; T1 showed improvement of dysphonia and T3 had esophageal speech development. Patients treated with chemotherapy or radiation therapy, smoker or non-smoker / drinker, with primary education and T1 stage developed esophageal voice and had dysphagia / dysphonia improved. Patients who have developed voice with electrolarynx worked in commerce or in the service sectors, age group 20-59 years with high school, nodes, metastasis and stage T4. The gestural/ writing and gestural development occurred more frequently in patients who had smoking and drinking habits and stage T3. Those who showed improvement of dysphonia had association with cordectomy (60 years or older) were working in the agricultural sector or other, with no schooling or had higher education and T2 stage. Conclusion: The optimization and diversification and positive results with new therapeutic procedures used in the treatment of these patients have showed challenges to the Speech Therapists, above all, encouraging them to intervene in areas that traditionally the effectiveness of their actions was not known to be recognized as well as evaluated. / Introdução: O câncer de cabeça e pescoço ocupa a sexta posição como mais freqüente em todo o mundo; 40% ocorrem na cavidade oral; 25% na laringe; 15% na faringe e 20% nos demais sítios anatômicos. Objetivos: Analisar a associação dos casos de câncer de cabeça e pescoço e o desfecho da reabilitação fonoaudiológica de pessoas com câncer da laringe. Materiais e Métodos: Estudo transversal, quantitativo por meio de levantamento de dados em prontuários de pacientes com câncer de cabeça e pescoço, atendidos no período de 1989 a 2015, no Hospital de Base de São José do Rio Preto/SP, a partir de três dimensões: sócio-demográficas, clínicas e de reabilitação fonoaudiológica. O primeiro estudo analisou a correlação para os tipos de câncer e variáveis (sexo, local de origem, faixa etária e escolaridade). O segundo estudo foi analisado por meio de técnicas univariadas e multivariadas. Dados qualitativos foram associados por meio da aplicação do teste qui-quadrado. A abordagem multivariada, através da aplicação da Análise de Correspondência Múltipla possibilitou relações entre as variáveis mais importantes no estudo. Resultados: No primeiro estudo: 52,7% homens com idade mediana de 56 anos; maior prevalência a partir dos 41 anos (82,2%); 64,3% eram de outros municípios do estado de São Paulo. Predomínio de tumores acometendo estruturas da cabeça e pescoço, presentes em 53,2% dos casos. No segundo estudo, quanto à reabilitação fonoaudiológica, 75,49% apresentaram alterações no sistema neurovegetativo, desenvolveram fala e voz (64,22%); destes, 22,55% a voz esofágica; 21,57%) desenvolvimento da comunicação escrita e gestual; a escolaridade apresentou associação significativa com o desfecho da Fonoterapia (P<0,001). A comunicação gestual foi mais frequente em pacientes sem escolaridade, a melhora da disfonia em pacientes com ensino fundamental, melhora da disfagia/disfonia e voz com eletrolaringe em pacientes com ensino médio. Pacientes com estádio de tumor T2 e T4 tiveram, em sua maioria, melhora da disfagia e da disfonia; T1 apresentaram melhora da disfonia e T3 tiveram desenvolvimento de voz esofágica. Pacientes tratados com quimio ou radioterapia, tabagista ou não tabagista/etilista, com ensino fundamental e o estádio T1 desenvolveram a voz esofágica e tiveram melhora da disfagia/disfonia. Pacientes que desenvolveram voz com eletrolaringe trabalhavam no comércio ou no setor de serviços, faixa etária de 20 a 59 anos, com ensino médio, nódulos, metástase e no estádio T4. O desenvolvimento gestual/escrita e gestual ocorreu de forma mais frequente em pacientes que apresentaram tabagismo e etilismo como hábitos e estádio T3. Os que obtiveram melhora da disfonia apresentaram correspondência com cordectomia (60 anos ou mais de idade) trabalhavam no setor agropecuário ou em outros, sem escolaridade ou com ensino superior e estádio T2. Conclusão: A otimização e diversificação e resultados positivos com novos procedimentos terapêuticos utilizados no tratamento destes pacientes têm colocado desafios aos Fonoaudiólogos, sobretudo, estimulando-os a intervir em áreas, que tradicionalmente a eficácia de suas ações não era sabidamente reconhecida e avaliada.