Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-04-02T13:47:38Z No. of bitstreams: 1 Rosane Borges Dias - Estudo do perfil... 2014.pdf: 2418992 bytes, checksum: 9a4f389957bc3f98114112321eee18b4 (MD5) / Made available in DSpace on 2014-04-02T13:47:38Z (GMT). No. of bitstreams: 1 Rosane Borges Dias - Estudo do perfil... 2014.pdf: 2418992 bytes, checksum: 9a4f389957bc3f98114112321eee18b4 (MD5) Previous issue date: 2014 / Universidade Federal da Bahia. SAlvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / A displasia epitelial oral (DEO) é um aspecto histológico descrito em lesões potencialmente malignas, cujos mecanismos relacionados a patogênese e potencial de transformação são pouco conhecidos. Sabendo-se que a via de sinalização Sonic Hedgehog(SHH)tem participação no desenvolvimento do carcinoma escamocelular de boca(CEB) e que as proteínas relacionadas a esta via de sinalização estão envolvidas nos mecanismos biológicos relacionados a iniciação e progressão de tumores humanos. O objetivo deste trabalho foi estudar a expressão das proteínas da via de sinalização SHH em DEO, a fim de contribuir para o conhecimento do perfil biológico desta lesão. Material e Métodos: As amostras de DEO foram revisadas e classificadas de acordo com o risco de malignidade descrito por Kujan et al.(2006) e OMS(2005). Vinte e cinco casos de DEO foram submetidos a reação imuno-histoquímica para as proteínas SHH, PTCH1, SUFU, HHIP, GLI1 e Ciclina D1(CCND1)utilizando o sistema polimérico AdvanceTM(Dako). Para fins comparativos, cinco casos de hiperqueratose, oito de hiperplasia fibrosa inflamatória(HFI) e quatro de mucosas não-neoplásica(MNN)também foram avaliados.Todos os casos foram analisados de acordo com os parâmetros semiquantitativos descritos por Gurgel et al.(2008)e os dados foram analisados usando Graph Pad Prism5.01. Resultados: Vinte e um(84%)DEO foram classificados como lesões de baixo risco e 4(16%)como alto risco. A proteína SHH foi predominante no citoplasma(n =14, sendo 56%) e a positividade de PTCH1 foi observada em membrana e citoplasma (n=23, 92%). As proteínas HHIP e SUFU foram observadas principalmente no citoplasma das células epiteliais e foram positivas em 17 (68%) e 11 (44%) das DEO, respectivamente. GLI1 foi positivo em 21 (84%), principalmente localizada nos núcleos das células epiteliais (n=12; 70,6%). A proteína CCND1 foi exclusivamente no núcleo 19(76%).Em DEO, os escores predominantes para SHH, PTCH1, HHIP, SUFU, GLI1 e CCND1 foram: 2+ (57,14%), 3+ (73,91%), 3+ (58,82%), 2+ e 3+ (36,36%), 3+ (90,48 %), 1+(47,37 %), respectivamente. Os casos de DEO exibiram maior expressão de HHIP(p=0,02) e GLI1(p=0,00), em comparação com hiperqueratose. Além disso, níveis elevados de PTCH1 (p=0,05), HHIP (p= 0,01) e CCND1 (p=0,00) foram observados em DEO em comparação com HFI. Ainda, uma maior expressão de PTCH(p=0,01) foi observada nos casos de DEO quando comparados com MNN. Conclusões: Os nossos resultados sugerem que a via SHH pode participar da patogênese da DEO e reforçam a relação desta cascata sinalizadora na carcinogênese oral. / Oral epithelial dysplasia (OED) is a histological aspect described in premalignant lesions and the mechanisms related to the pathogenesis and malignant progression are poorly understood. It is known that Sonic Hedgehog (SHH) signaling pathway participates in the development of oral squamous cell carcinoma, and proteins related to this cascade are involved in biological mechanisms related to the initiation and progression of human tumors. The aim of this study was to investigate SHH signaling molecules in OED, in order to contribute to the knowledge of the biological profile of this lesion. Methods: Samples of OED were reviewed and classified according to the risk of malignancy described by Kujan et al. (2006) and WHO (2005). Twenty five cases of DEO were to submitted to immunohistochemical reactions for SHH, PTCH1, SUFU, HHIP, GLI1 and Cyclin D1 (CCND1) proteins using AdvanceTM polymer system (Dako). For comparative purposes, five cases of hyperkeratosis, eight inflammatory fibrous hyperplasia (IFH) and four non- neoplastic (NNM) mucosa were also evaluated. All OED were analyzed according to the semi-quantitative parameters described by Gurgel et al. (2008) and the data was analyzed using Graph Pad Prism 5.01. Results: Twenty- one (84%) OED were classified as low risk lesions and 4 (16%) as high risk. SHH protein was predominant in cytoplasm (n=14; 56%) and PTCH1 positivity was described in both membrane and cytoplasm (n=23; 92%). HHIP and SUFU proteins were observed in cytoplasm of epithelial cells and were positive in 17 (68%) and 11 (44%) OED, respectively. GLI1 protein was positive in 21 (84%), mainly located in the cells nuclei (n=12; 70.6%). CCND1 protein was exclusively in the nucleus 19 (76%). The predominant scores for SHH, PTCH1, HHIP, SUFU, GLI1 and CCND1 were: +2 (57.14%), +3 (73.91%), +3 (58.82%), +2 and +3 (36.36%), +3 (90.48%), +1 (47.37%), respectively. OED sample had higher levels of HHIP (p=0.02) and GLI1 (p=0.00) as compared to hyperkeratosis. Furthermore, high levels of PTCH (p=0.05), HHIP (p=0.01) and CCND1 (p=0.00) were observed in OED as compared to IFH OED. Also, a high level of PTCH (p= 0.01) was observed in OED as compared to NNM. Conclusions: Our results suggest that the SHH pathway may participate in the pathogenesis of DEO and corroborates to the relationship of this signaling cascade in oral carcinogenesis.

No description available.

Magister Scientiae Dentium - MSc(Dent) / Oral epithelial dysplasia (OED) is a growth anomaly which occurs as a result of atypical, abnormal proliferation and a change in the architecture and cytological features of cells of epithelial origin, which ultimately results in the formation of a lesion with disturbed differentiation and maturation The purpose of this study was to describe the OED cases diagnosed at Tygerberg Oral health centre in a 7-year period between 2012 and 2019. The patients’ medical records from Tygerberg Oral Health Centre and National Health Laboratory Service (NHLS) were reviewed. All diagnosed cases of OED were identified and the data retrieved for further assessment and comparison. The individual medical records and follow up data were assessed. Seventy cases of OED were diagnosed in the period assessed. Of those 70 cases, the median age was 58 and the interquartile range was from 48 – 62. Thirty-six of the diagnosed patients were female and thirty-four were males. The majority of lesions diagnosed with OED were found on the tongue, floor of the mouth (FOM) and buccal mucosa. Majority of the lesions were found in non-smokers and non-alcohol consumers. These two categories both presented with mild cases of OED. From the results, it was derived that OED has no intra-oral location predilection. Moreover, OED is not directly associated with smoking.

No description available.

Made available in DSpace on 2014-12-17T15:32:31Z (GMT). No. of bitstreams: 1 ManoelAGN_tese.pdf: 5283581 bytes, checksum: 65511a1dd2487deff44e8db44d2a0cf5 (MD5) Previous issue date: 2006-08-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The objective of this study was perform by the streptoavidin-biotin technique an immunohistochemical analysis of ?2?1, ?3?1e ?5?1 integrins in 11 normal oral mucosa (NOM), 16 oral inflammatory fibroepithelial hyperplasia (OIFH) and 25 oral epithelial dysplasia (OED) (16 mild, 2 moderates and 7 severe), to determine if exists qualitative alteration in the expression of these integrins and if this guard relation with the oral epithelial modifications. It was observed that for the ?2?1 integrin the majority of the sample showed a predominantly intense labeling diffusely distributed in the intercellular contacts and the cytoplasm of cells of the basal and suprabasal layers, without difference of this profile between the different types of specimens, however with a trend to weak or loss of expression in 21.1% of the OEDs, being all the specimens that had not expressed this heterodimer, severe OEDs. For the ?3?1 integrin the majority of the sample showed a weak or absent labeling in basal layer. The ?5?1 integrin showed a predominant strong diffuse labeling in the intercellular contacts and cytoplasm in the suprabasal layer, with difference only in the labeling intensity between the types of specimens, inhabiting this difference in the OEDs, where 12 (48%) specimens had shown a weak labeling. It was concluded that the evaluated integrins can be involved in the cell-cell, cell-ECM interactions modulating the cellular differentiation and maintenance of the epithelial structural arrangement. The variable expression of the ?5?1 integrin in the OEDs, could suggest, respectively, a role of this molecule in the cellular survival, with intention to perpetuate the modified phenotype in these lesions, or a suppressor role on the modified phenotype due to lack of interaction of this molecule with the fibronectina of the MEC / Este estudo se prop?s analisar atrav?s da t?cnica da estreptoavidina-biotina a express?o imuno-histoqu?mica das integrinas ?2?1, ?3?1e ?5?1 em 11 esp?cimes de mucosa oral normal (MON), 16 de hiperplasia fibroepitelial inflamat?ria oral (HFIO) e 25 de displasia epitelial oral (DEO) (16 leves, 2 moderadas e 7 graves), procurando determinar se existe altera??o qualitativa na express?o destas integrinas e se a mesma guarda rela??o com as modifica??es sofridas pelo epit?lio oral. Para a integrina ?2?1 a maioria dos esp?cimes exibiu uma marca??o predominantemente intensa e difusa nos contatos intercelulares e no citoplasma celular das camadas basal e suprabasal, sem diferen?a desse perfil entre os diferentes tipos de esp?cimes, por?m com uma tend?ncia a fraca ou perda da express?o em 21.1% das DEOs, sendo todos os esp?cimes que n?o expressaram marca??o para este heterod?mero DEOs graves. Para a integrina ?3?1 a maioria da amostra exibiu uma marca??o fraca ou ausente predominantemente em camada basal. A integrina ?5?1 exibiu uma forte marca??o difusa nos contatos intercelulares e citoplasm?tica na camada suprabasal, com diferen?a apenas na intensidade de marca??o entre os tipos de esp?cimes, residindo essa diferen?a nas DEOs, onde 12 (48%) esp?cimes exibiram uma fraca marca??o. Concluiu-se que as integrinas avaliadas podem estar envolvidas nas intera??es c?lula-c?lula e c?lula-MEC que garantem a diferencia??o celular e manuten??o do arranjo estrutural tecidual. A vari?vel express?o da integrina ?5?1 nas DEOs, poderia sugerir, respectivamente, um papel dessa mol?cula na sobrevida celular, com o intuito de perpetuar o fen?tipo alterado nessas les?es, ou uma a??o supressora desse fen?tipo devido ? falta de intera??o desta mol?cula com a fibronectina da MEC

Made available in DSpace on 2014-08-20T14:30:13Z (GMT). No. of bitstreams: 1 Dissertacaoo_Deise_de_ Avila_Silva.pdf: 596277 bytes, checksum: bb38f7b6e8b73ab071ecabe2d943800c (MD5) Previous issue date: 2012-09-14 / This study aims to evaluate the immunohistochemical expression of antibodie MAGE-(Y18) in potentially malignant oral lesions and malignant lesions in patients with or without factor risk, and also to check the interexaminers variability on histological classification of oral epithelial dysplasia. Paraffin-embedded samples of 20 cases of severe dysplasia/carcinoma in situ and 20 cases of intraoral squamous cell carcinoma (SCC) were used in the study, and in both groups the samples had been distributed between patients with and without other risk factors associated with the occurrence of injury (tobacco and alcohol). The positive immunohistochemical expression of MAGE(Y-18) was defined by a cytoplasmic staining pattern, and it was used a scoring system considering the homogeneity of the reaction. In order to verify the interexaminer variability when performing a histological classification of oral epithelial dysplasia, 75 cases of potentially malignant oral lesions were selected from a referral service in oral disease. Slides were read independently and blindly by three pathologists in two stages. In the first stage it was made available to examiners the slides stained with H & E along with the clinical information of each case, and pathologists had to classify the lesions: no dysplasia, mild dysplasia, moderate dysplasia, severe dysplasia or carcinoma in situ.In the second stage, it was not given access to clinical information to the examiners, and they had to classify slides into two categories: low risk (non-dysplastic lesions / mild dysplasia) and high risk (moderate or severe dysplasia / carcinoma in situ). . The results were positive in 4/20 PML and 17/20 SCC. Through the Kruskal-Wallis test, it was observed a statistically significant difference (p<0.05) between groups of CPB and the group of potentially malignant lesions (PML) without the risk factor. The Mann-Whitney test found a statistically significant difference between carcinomas and potentially malignant lesions (p<0.001). The Fisher Exact test showed no statistically significant difference between the lesions that had the same histological diagnosis when compared in subgroups of associated risk factor (p=1). Detection of MAGE antigen may be useful in identifying LPM that has a higher risk of progression to invasive SCC, but it seems to be unrelated to exposure to popular risk factors The agreement between the examiners and the gold standard ranged from low to moderate, regardless of the classification system that was used. In the first stage, the intraclass correlation coefficient showed a moderate agreement between examiners 1 and 3 (r = 0.479 and r = 0.544) and, a low agreement of the examiner 2 (r = 0.384). In the second phase, it was observed a moderate agreement between examiners 2 and 3 and the gold standard (k = 0.433 k = 0.422) and, a low concordance between the examiner 1 and the gold standard (k = 0.186).Taking into account that grading dysplasia is a subjective process and still there is no test that outperforms the histological observation on diagnosis of oral epithelial dysplasia, it is understood that the process of grading made by two or more examiners should be encouraged, in order to assist in defining more precisely the diagnostics / O objetivo deste trabalho foi avaliar a expressão imuno-histoquímica do MAGE (Y-18) em LPM e malignas de pacientes com e sem fator de risco associado, bem como verificar a variabilidade interexaminadores na classificação histológica das displasias epiteliais orais. Foram utilizadas amostras incluídas em parafina de 20 casos de displasia severa/carcinoma in situ e 20 casos de CEC intraoral, sendo que em cada grupo as amostras estavam distribuídas entre pacientes com e sem fator de risco associado à ocorrência da lesão (tabaco e álcool). A expressão imuno-histoquímica positiva de MAGE (Y-18) foi definida por um padrão de coloração citoplasmático, sendo utilizado um sistema de pontuação considerando a homogeneidade da reação. Para classificar as displasias epiteliais orais, 75 casos de lesões orais potencialmente malignas foram selecionados de um serviço de referência em patologia bucal. Três patologistas analisaram as lâminas de forma independente e cega em dois momentos.Na primeira etapa foram disponibilizadas aos examinadores as lâminas coradas em H&E juntamente com as informações clínicas de cada caso e os patologistas classificaram as lesões em sem displasia, displasia leve, moderada, severa ou carcinoma in situ. Na segunda etapa, os avaliadores não tiveram acesso às informações clínicas e classificaram as lâminas em duas categorias: baixo risco (lesão não displásica/displasia leve) e alto risco (displasia moderada/severa/carcinoma in situ). A análise das reações imuno-histoquímicas demonstrou positividade em 4/20 LPM e 17/20 CEC. Pelo teste de Kruskall-Wallis observou-se diferença estatisticamente significativa (p<0,05) entre os grupos de CEC e o grupo das lesões potencialmente malignas sem fator de risco. O teste de Mann-Whitney verificou diferença estatisticamente significativa entre os carcinomas e as lesões potencialmente malignas (p<0.001). O teste Exato de Fischer não demonstrou diferença estatisticamente significativa entre as lesões de mesmo diagnóstico histológico quando comparadas nos subgrupos de fator de risco associado (p=1). Nossos resultados sugerem que a detecção do antígeno MAGE pode ser útil na identificação de LPM com maior risco de progressão para o CEC invasivo, mas parece não ter relação com a exposição aos fatores de risco mais conhecidos. Quando na classificação das displasias, independente do sistema de classificação utilizado, a concordância entre os avaliadores e o padrão ouro variou de fraca a moderada.Na primeira etapa, o Coeficiente de Correlação Intraclasse demonstrou uma concordância moderada entre os avaliadores 1 e 3 (r=0,479 e r=0,544) e uma concordância baixa do avaliador 2 (r=0,384). No segundo momento observou-se uma concordância moderada entre os examinadores 2 e 3 e o padrão ouro (k=0,433 e k=0,422) e uma baixa concordância entre o avaliador 1 e o padrão ouro (k=0,186). Tendo em vista que a graduação da displasia é um processo subjetivo, e que ainda não dispomos de nenhum exame que supere a observação histológica no diagnóstico das displasias epiteliais orais, entendemos que o processo de graduação entre dois ou mais observadores deve ser incentivado, a fim de auxiliar na definição mais precisa do diagnóstico