Made available in DSpace on 2014-12-17T15:32:27Z (GMT). No. of bitstreams: 1 CristinaRFA.pdf: 1625942 bytes, checksum: 99d50db14437c5ea0e3022e4da576321 (MD5) Previous issue date: 2009-03-06 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Bone morphogenetic proteins (BMPs) are cytokines involved in proliferation and angiogenesis of many kind of human cancer. The present study analyzed the immunohistochemical expression of BMP-2, BMPR-II, BMPR-IA and endoglin (CD105) and their relationship with the biological behavior and local angiogenesis in tongue oral squamous cells carcinoma (SCC). The sample consisted of 25 cases of tongue SCC without metastasis, 25 tongue SCC with metastasis and 25 cases of Inflamatory Fibrous Hyperplasia (IFH).The histological grade of malignancy proposed by Bryne (1998), adapted by Miranda (2002) was used to classify all tongue SCC cases. Score 0 was attributed to absent-weak immunoexpression and score 1 for strong immunostaning and pattern of distribution was focal or diffuse. Microvessel counts (MVC) was established for CD105. Most of the patients with tongue SCC was male. The principal age in tongue SCC without metastasis was over 65 years and in tongue SCC with metastasis was between 45-65 years. There were predominance of stage II in TNM and in the specimens with high-grade, independent of studied group. For BMP-2, 56% of tongue SCC without metastasis and 72% tongue SCC with metastasis exhibited score 1 while the IFH showed secore 0 in 72% of the cases, with statistical association (p=0,007). Considering the BMPR-II, 52% of tongue SCC without metastasis exhibited score 0; 56% tongue SCC with metastasis and 60% IFH showed score 1. The majority cases of BMPR-IA demonstrated score 1 and 100% of CD105 exhibited strong immunoexpression in tongue SCC. Regarding the pattern distribution, it was noted a tendency to diffuse pattern for the proteins in all groups. The means of MVC were similar in tongue SCC without metastasis (32,91) and in tongue SCC with metastasis (32,05), however existed statistical difference with IFH (p<0,001). There was statistical association of BMP-2 expression with BMPR-II (p=0,008), BMPR-IA (p=0,006) and CD105 (p=0,046). An association between TNM and BMP-2 immunoexpression and their receptors was not detected, nevertheless this association was found with MVC (p=0,047) whose averages were higher for the stages II (35,97) e IV (35,69). No association between histological grading and these proteins was observed. This study suggests that the superexpression of BMP-2 signaling pathways acts on cell proliferation in tongue SCC and can be implicated with more invasive potential. Additionaly, the CD105 is a potent biological marker of neovascularization in this neoplasm and their association with BMP-2 and BMPR-IA receptor, showed that this type of cancer in BMP-2 is presented as pro-angiogenic in the metastatic process / As BMPs (prote?nas morfogen?ticas ?sseas) s?o citocinas relacionadas com a prolifera??o e angiog?nese em diversos tipos de c?ncer humano. Com este trabalho foi analisada a express?o imunoistoqu?mica das prote?nas BMP-2, BMPR-IA, BMPR-II e endoglina (CD105), correlacionando-a com o comportamento biol?gico e a angiog?nese local nos carcinomas epiderm?ides de l?ngua (CEL). A amostra foi composta de 25 casos de CEL sem met?stase (CELSM), 25 CEL com met?stase (CELCM) graduados segundo Bryne (1998) e adaptado por Miranda (2002), al?m de 25 casos de hiperplasia fibrosa inflamat?ria (HFI), utilizado como grupo controle. Foi utilizado escore 0 para marca??o ausente-fraca e 1 para forte; tipo de distribui??o focal ou difuso. Adicionalmente, para o CD105 foi realizada a contagem microvascular (MVC). A maior parte dos pacientes com CEL foi do sexo masculino, no grupo CELSM a faixa et?ria foi maior que 65 anos e o CELCM se encontrou entre 45-65 anos; houve predom?nio do est?gio II do TNM, assim como de esp?cimes de alto grau, independente do grupo estudado. Para BMP-2, 56% dos CELSM e 72% dos CELCM exibiram escore 1, enquanto a HFI exibiu 72% de escore 0, apresentando associa??o estat?stica (p=0,007). Para BMPR-II 52% dos CELSM exibiram escore 0; 56% CELCM e 60% da HFI escore 1 e no BMPR-IA ocorreu uma predomin?ncia de escore 1 e para o CD105 100% de marca??o forte nos CEL. Quanto ao tipo de distribui??o notou-se tend?ncia de distribui??o difusa de todas as prote?nas, em todos os grupos. Observaram-se, para MVC, m?dias muito semelhantes entre os CELSM (32,91) e os CELCM (32,05) exibindo, contudo, diferen?a estat?stica com as HFI (p<0,001).Observa-se uma associa??o estat?stica da BMP-2 com a BMPR-II (P=0,008), BMPR-IA (p=0,006) e o CD105 (0,046). N?o se observou associa??o entre o TNM e a imunoexpress?o da BMP-2 e seus receptores, por?m foi encontrada com a MVC (p=0,047), cujas maiores m?dias foram para os est?gios II (35,97) e IV (35,69), tal como n?o ocorreu associa??o entre a grada??o histol?gica e as prote?nas. Conclui-se que a superexpress?o da via de sinaliza??o da BMP-2 atua na prolifera??o celular, contribuindo para maior invasividade do CEL. O CD105 ? um potente marcador de neovasculariza??o deste neoplasma e sua associa??o com a BMP-2 e o receptor BMPR-IA, mostra que neste tipo de neoplasia a BMP-2 se apresenta como pr?-angiog?nico no processo metast?tico

Made available in DSpace on 2014-12-17T15:32:31Z (GMT). No. of bitstreams: 1 RosileneCS.pdf: 376311 bytes, checksum: 8a0459347381c3b197002ddd72f02225 (MD5) Previous issue date: 2005-11-04 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Oral squamous cell carcinoma (OSCC) is the most common malignancy in oral cavity and human papillomavirus (HPV) may have an important role in its development. The aim of this experiment was to investigate the HPV DNA and viral types in 90 cases of OSCC. Moreover, a comparative analysis between the cases of OSSC with and without HPV DNA was performed by using cell cycle markers p21 and pRb in order to detect a possible correlation of these proteins and HPV infection. DNA was extracted from paraffin embedded tissue and amplified by PCR (polymerase chain reaction) with primers PCO3+ e PCO4+ for a fragment of human &#946;-globin gene. After this procedure, PCR for HPV DNA detection was realized using a pair of generic primers GP5+ e GP6+. Immunohistochemical study was performed by streptoavidin-biotin technique and antibodies against p21 and pRb proteins were employed. Eighty-eight cases were positive for human &#946;-globin gene and HPV DNA was found in 26 (29.5%) of then. It could not be detected significant correlation between HPV and age, sex and anatomical sites of the lesion. The most prevalent viral type was HPV 18 (80.8%). Regarding the immunohistochemical analysis, it was detected significant association between HPV presence and pRb immunoexpression (p=0,044), nevertheless, the same was not observed in relation to p21 protein (p =0,416). It can be concluded that the low detection of HPV DNA in OSCC by the present experiment suggests a possible role of the virus in the development and progression in just a subset of this disease / O carcinoma epiderm?ide oral ? a neoplasia maligna mais freq?ente da cavidade oral e o papilomav?rus humano (HPV) parece ter um relevante papel na indu??o desta les?o. Neste trabalho investigou-se o DNA do HPV e tipos virais em 90 casos de carcinoma epiderm?ide oral (CEO). Realizou-se tamb?m uma an?lise comparativa entre os grupos de CEO com DNA do HPV e sem o DNA do v?rus, empregando-se os marcadores do ciclo celular p21 e pRb, a fim de estabelecer poss?vel correla??o entre a express?o imuno-histoqu?mica dessas prote?nas e a infec??o pelo HPV. O DNA foi extra?do de tecido emblocado em parafina e amplificado por PCR (rea??o em cadeia da polimerase) com um par de primers designados PCO3+ e PCO4+ para um fragmento do gene da &#946;-globina humana. Posteriormente, realizou-se PCR para detec??o do DNA de HPV utilizando-se um par de primers gen?ricos designados GP5+ e GP6+. A tipagem viral foi realizada pela hibridiza??o dot blot. No m?todo imuno-histoqu?mico utilizou-se a t?cnica da streptavidina-biotina com um painel de anticorpos monoclonais para as prote?nas p21 e pRb. Dos 88 casos positivos para o gene da &#946;-globina humana, em 26 (29,5%) foi detectado o DNA do HPV. N?o houve associa??o significativa entre o HPV e as vari?veis idade e sexo dos pacientes e localiza??o anat?mica da les?o. O tipo viral prevalente foi o HPV 18 (80,8%). Quanto ? an?lise imuno-histoqu?mica, foi observada associa??o estatisticamente significativa entre a presen?a do HPV e a express?o imunohistoqu?mica de pRb (p=0,044), entretanto, n?o houve qualquer diferen?a estatisticamente significativa entre a express?o da prote?na p21 e a presen?a do v?rus (p =0,416). P?de-se concluir que o baixo percentual de detec??o do DNA do HPV no carcinoma epiderm?ide oral no presente trabalho, sugere uma poss?vel participa??o do HPV no desenvolvimento e progress?o de apenas um subgrupo dessas les?es

Made available in DSpace on 2014-12-17T15:32:33Z (GMT). No. of bitstreams: 1 FernandaFL.pdf: 1297057 bytes, checksum: 8488c96c7464744f8dcbec706cd89a77 (MD5) Previous issue date: 2007-09-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The adhesion molecules E-cadherin and &#946;-catenin have been studied as possible markers to distinguish carcinomas with and without metastatic potential. The objective of this research was to study the imunohistochemistry expression of the E-cadherin and &#946;-catenin in oral squamous cell carcinoma (OSCC), aiming to contribute for the better understanding of the biological behavior of this lesion. The sample consisted of 30 cases of OSCC, being 15 of tongue and 15 of lower lip. The profile and intensity of labeling and semi quantitative analysis of the percentage of immunopositive tumoral cells in membrane for E-cadherin and &#946;-catenin had been related with the anatomical localization of the lesion, the presence or not of nodal metastasis and the histological grade of malignancy in the invasive front area of the tumor. It was registered the presence or not of cytoplasmic and nuclear labeling of the &#946;-catenin. The results had been submitted to the statistical analysis, being used the Mann-Whitney Test, the Fisher Test and the Spearman Correlation Coefficient (&#945;=0, 05). The results showed that the expression in membrane for E-cadherin and &#946;-catenin was, predominantly, the heterogeneous profile in the lower lip and tongue carcinomas, as well as in the cases with and without nodal metastasis. It was not observed significant statistical difference between expression profile and amount of immunopositive cells for E-cadherin, &#946;-catenin and the anatomical localization of the lesion and for the presence or not of nodal metastasis. However, there was significant difference of the reduced expression of these proteins with the high score of malignancy. It was verified that the expression of the &#946;-catenin in cytoplasm was present in 22 (73.33%) of the 30 analyzed cases, and 6 cases (20%) showed nuclear expression. The statistical analysis detected significant association between the expression of the &#946;-catenin in the cytoplasm with the histological grade of malignancy, being this molecule more frequently present in the cytoplasm in the cases of high score of malignancy. It was concluded that the reduced immunoexpression of these proteins in membrane can be related with the lowest cellular differentiation, as well as with the pattern of invasion in nests and isolated cells, demonstrated in the cases of OSCC with high histological grade of malignancy / As mol?culas de ades?o E-caderina e &#946;-catenina t?m sido estudadas como poss?veis marcadores para distinguir carcinomas com e sem potencial metast?tico. O objetivo desta pesquisa foi estudar a express?o imuno-histoqu?mica da E-caderina e &#946;-catenina em carcinoma epiderm?ide oral (CEO), visando contribuir para uma melhor compreens?o do comportamento biol?gico desta les?o. A amostra constou de 30 casos de CEO, sendo 15 de l?ngua e 15 de l?bio inferior. O padr?o e intensidade de marca??o e a an?lise semiquantitativa do percentual de c?lulas tumorais imunopositivas em membrana para E-caderina e &#946;-catenina foram relacionados com a localiza??o anat?mica da les?o, a presen?a ou n?o de met?stase nodal e a grada??o histol?gica de malignidade no front de invas?o tumoral. Tamb?m foi registrada a presen?a ou n?o de imunomarca??o citoplasm?tica e nuclear da &#946;-catenina. Os resultados foram submetidos ? an?lise estat?stica, sendo utilizados o Teste de Mann-Whitney, o Teste Exato de Fisher e o Coeficiente de correla??o de Spearman (&#945;=0,05). Os resultados mostraram que a express?o em membrana para E-caderina e &#946;-catenina exibiram, predominantemente, o padr?o heterog?neo nos carcinomas de l?bio inferior e nos de l?ngua, assim como nos casos com e sem met?stase nodal. Aplicados os testes estat?sticos, observou-se que n?o houve diferen?a significativa entre o padr?o de express?o e a quantidade de c?lulas imunopositivas para E-caderina e &#946;-catenina e a localiza??o anat?mica da les?o e para a presen?a ou n?o de met?stase nodal. Por?m, verificou-se diferen?a estatisticamente significativa da express?o reduzida destas prote?nas com o alto escore de malignidade. Observou-se que a express?o da &#946;-catenina em citoplasma estava presente em 22 (73,33%) dos 30 casos analisados, sendo que em 6 casos (20%) houve a express?o em n?cleo. Ap?s a an?lise estat?stica, foi detectada uma associa??o significativa entre a express?o da &#946;-catenina no citoplasma com a grada??o histol?gica de malignidade, estando esta mol?cula mais freq?entemente presente no citoplasma nos casos de alto escore de malignidade. Conclui-se que a imunoexpress?o reduzida destas prote?nas em membrana pode estar relacionada com o menor grau de diferencia??o celular, bem como com o padr?o de invas?o em ninhos e em c?lulas isoladas, demonstrados nos casos de CEO de alto escore

Made available in DSpace on 2014-12-17T15:32:33Z (GMT). No. of bitstreams: 1 AntonioLAP.pdf: 801979 bytes, checksum: bfcf5910a257b5978efceb008f0c1016 (MD5) Previous issue date: 2006-09-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The unpredictable biologic behavior of the oral squamous cells carcinoma has determined extensive research on the evolution of such tumor. Due to the existing relation between the outer cell matrix and the tumor cells, the integrins have been used as markers in the predictive study of the cell behavior. This study aims to analyze immunohistochemically the expression of the integrin ?2?1, ?3?1, and ?5?1 connections for the collagen, the laminin and the fibronectin respectively in 15 cases of squamous cells carcinoma from the lower lip and 15 from the tongue, with different scores of malignance grading. A predominantly diffuse, cytoplasm and granular immunological marking was observed in the majority of the analyzed cases. According to the marking intensity, integrin ?2?1 appeared positive in 80% of the lip and in 93,3% of the tongue cases. The immunological reactivity of integrin ?3?1 was classified as positive in 60% of both the tongue and lip cases. For this integrin, 20% and 33.3% of the tongue and lip cases, respectively, were negative. In relation to integrin ?5?1 the intensity was classified as positive in 53,3% of the cases and strongly positive in 46,7% of those located in the lip. In the tongue carcinomas, the intensity was positive in 46,7% of the cases and strongly positive in 53,3%. The statistic analysis did not show any significant differences or correlation of expression between these integrins nor between the anatomical sites or between different scores of malignancy grading. The expressive immunological marking of the integrins, ?2?1, ?3?1, and ?5?1 in the studied cases of squamous cell carcinomas leads us to think of a great participation of these proteins in oral carcinogenesis; however, our results do not allow us to correlate its expression as an indicator of variations in the biological behavior of this neoplasia / A imprevisibilidade do comportamento biol?gico do carcinoma epiderm?ide oral vem justificando um grande n?mero de pesquisas utilizando biomarcadores que possam contribuir para um melhor entendimento do curso evolutivo dessa neoplasia. Por estarem envolvidas em rela??es entre as c?lulas tumorais e constituintes da matriz extracelular, as integrinas v?m sendo estudadas como poss?veis marcadores preditivos desse comportamento. Este estudo se prop?s a analisar, atrav?s do m?todo da imunohistoqu?mica, a express?o das integrinas ?2?1, ?3?1 e ?5?1, ligantes para o col?geno, laminina e fibronectina respectivamente, em 15 casos de carcinoma epiderm?ide de l?bio inferior e 15 de l?ngua, com diferentes escores de malignidade histol?gica. Observou-se uma imunomarca??o predominantemente difusa, citoplasm?tica e granular na maioria dos casos analisados. Quanto ? intensidade de marca??o, a integrina ?2?1 mostrou-se de forma positiva em 80% dos casos de l?bio e em 93,3% dos de l?ngua. A imunorreatividade da integrina ?3?1 foi classificada como positiva em 60% dos casos de l?bio e de l?ngua. Para esta integrina, 20% e 33,3% dos casos de l?bio e l?ngua, respectivamente, mostraram-se negativos. J? com rela??o ? integrina ?5?1a intensidade foi classificada como positiva em 53,3% dos casos e fortemente positiva em 46,7% daqueles localizados em l?bio. Nos carcinomas de l?ngua, a intensidade mostrou-se positiva em 46,7% dos casos e fortemente positiva em 53,3%. A an?lise estat?stica n?o demonstrou diferen?as nem correla??es significativas da express?o dessas integrinas nem entre os s?tios anat?micos, nem entre diferentes escores de grada??o histol?gica de malignidade. A expressiva imunomarca??o das integrinas ?2?1, ?3?1e ?5?1 nos casos de carcinomas epiderm?ides estudados nos leva a sugerir uma ampla participa??o dessas prote?nas na carcinog?nese oral; no entanto, nossos resultados n?o nos permitem correlacionar sua express?o como indicador de varia??es no comportamento biol?gico desta neoplasia

Made available in DSpace on 2014-12-17T15:32:18Z (GMT). No. of bitstreams: 1 CyntiaCPC.pdf: 2470782 bytes, checksum: 4619c7ffcab85bffa54a732d30786d99 (MD5) Previous issue date: 2010-02-24 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Currently, bone morphogenetic proteins (BMPs) have effective participation in the growth of malignancies. Knowing that there are few studies involving BMPs and oral squamous cell carcinoma, this work constitutes an immunohistochemical study of BMP-2, BMPR IA and BMPR II in squamous cell carcinomas (SCC) of the lower lip relating to the clinical and pathological aspects of this lesion. The sample consisted of 40 cases of SCC of the lower lip, being 20 cases of SCC of the lower lip with regional metastasis and 20 cases without metastasis. We evaluated the intensity of expression (score 1 to mark absent / weak, score 2 for high ) and was found the percentage of labeled cells, where the score was 1 cases with 0 to 50% of positive cells, score 2 with 51 to 75% of positive cells, and score 3 more than 75% of positive cells. The sample comprised 72.5% of men with a mean age of 65.8 years, there was a predominance of stage II and 52.5% of the carcinomas were classified as low grade, being carcinoma with metastasis presenting most cases (70%) as carcinomas of high malignancy grade (p = 0.004). The largest number of cases of SCC of the lower lip that were in stages I / II (61, 9%) were classified as carcinomas of low grade malignancy and carcinomas in stages III / IV were classified as high-grade tumors (p = 0, 024). The BMP-2 showed strong intensity of immunostaining in 82.5%, BMPR-IA showed 55% of cases with an intensity of immunostaining absent / weak and BMPR-II showed 85% of cases with an intensity of immunostaining absent / weak. Only the protein BMPR-IA were significantly associated with all clinic-pathological parameters studied, metastasis (p <0.001), TNM (p <0.001) and histological grade of malignancy with (p = 0.028). The percentage of positive cells, all markers showed the highest number of cases with more than 75% of positive cells (score 3) and only BMPR-II showed statistical difference when related to the presence and absence of metastasis (p = 0.049 ). We conclude that there is disturbance in the BMP signaling pathway in EC-mediated lower lip and that high expression of BMP-2 associated with the expression of BMPR-IA and BMPR-II are associated with metastasis in carcinoma / Atualmente as prote?nas morfogen?ticas do osso (BMPs) t?m efetiva participa??o no crescimento de neoplasias malignas. Sabendo que s?o escassos os trabalhos envolvendo BMPs e o carcinoma epiderm?ide oral, este trabalho realizou um estudo imunoistoqu?mico da BMP-2, BMPR IA e BMPR II em carcinomas epiderm?ides (CE) de l?bio inferior relacionando com os aspectos clinico-patol?gicos desta les?o. A amostra constou de 40 casos de CE de l?bio inferior, sendo 20 casos de CE de l?bio inferior com met?stase linfonodal regional e 20 casos sem met?stase. A grada??o histol?gica de malignidade foi realizada no front invasivo da les?o. Foi avaliada a intensidade de express?o (escore 1 para marca??o ausente/ fraca e escore 2 para marca??o forte), bem como foi verificado a porcentagem de c?lulas positivas, onde o escore 1 era os casos com 0 a 50% das c?lulas positivas; escore 2 com 51 a 75% das c?lulas positivas; e escore 3 com mais de 75% das c?lulas positivas. A amostra foi composta por 72,5% de homens com a m?dia de idade de 65,8 anos, houve um predom?nio do est?gio II e 52,5% dos carcinomas foram classificados como de baixo grau, sendo os carcinomas com met?stase regional apresentando a maioria dos casos (70%) como carcinomas de alto grau de malignidade (p =0,004). O maior n?mero de casos de CE de l?bio inferior que estavam nos est?gios I/ II (61, 9%) foi classificado em carcinomas de baixo grau de malignidade e os carcinomas nos est?gios III/ IV foram classificados em alto grau de malignidade (p =0, 024). A BMP-2 apresentou intensidade da imunomarca??o forte em 82,5%, BMPR-IA observou-se 55% dos casos com intensidade de imunomarca??o ausente/ fraca e a BMPR-II revelou 85% dos casos com intensidade de imunomarca??o ausente/ fraca. Apenas a prote?na BMPR-IA apresentou associa??o estatisticamente significante com todos os par?metros clinico-patol?gicos estudados, met?stase (p<0,001), TNM (p<0,001) e grada??o histol?gica de malignidade com ( p=0,028). Quanto ? porcentagem de c?lulas positivas, todos os marcadores apresentaram o maior n?mero de casos com mais de 75% das c?lulas positivas (escore 3) e apenas a BMPR-II apresentou diferen?a estat?stica quando relacionada com a presen?a e aus?ncia de met?stase (p=0,049). Conclui-se que existe dist?rbio na via de sinaliza??o BMP-mediada no CE de l?bio inferior e que a alta express?o da BMP-2 associada com a express?o da BMPR-IA e BMPR-II est?o relacionadas com a met?stase neste carcinoma

Made available in DSpace on 2014-12-17T15:32:21Z (GMT). No. of bitstreams: 1 EdilmarMS_DISSERT.pdf: 790528 bytes, checksum: 570c185c018d55b199d467de6ca18465 (MD5) Previous issue date: 2012-02-09 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The most common malignant neoplasm of the oral cavity and oropharynx are squamous cell carcinoma. Injuries to the same stage and subjected to the same treatment protocol have sometimes different evolutionary courses. The scope of this study was to investigate, through a retrospective cohort, associations between the number of CD8 + T cells and natural killer, identified immunohistochemically in the inflammatory infiltrate in a series of cases of oral squamous cell carcinoma and orofaringeano, and the level of tumor response to radiotherapy and chemotherapy, overall survival and relapse-free survival of patients. We identified 54 patients with unresectable disease were treated exclusively with radiotherapy and chemotherapy. The median follow-up was 22 months. The sample was characterized by the predominance of male subjects, median age 60 years, all were smokers. The most frequent site was the tongue and 81.5% were in stage IV. Patients with disease in the oral cavity had a worse response to treatment (p = 0.006), worse relapse-free survival (p = 0.007), worse overall survival (p = 0.007). The advanced T stage was shown a negative prognostic factor (p= 0.006) for the clinical treatment response made. Immunohistochemistry was performed to select CD8 + cells (anti-CD8) and NK cells (anti-CD57). Lymphocytes positive and negative markings were counted using the program ImageJ ?. Two groups were created for each marking evaluated: Group I patients with more than 50% cells positive, Group II: less than 50% of labeled cells. For CD8 + cells detected in 38 (70.3%) of Group I were CD8 + and 16 (29.7%) Group II CD8 +. For NK cells, 26 (48.15%) Group I NK and 28 (51.85%) Group II NK. Regarding the clinical response to treatment, we observed that 39% of patients achieved a complete response and 25.9% remained without recurrence at the end of follow-up. These results were better in Group I CD8 + (p = 0.2). Identified that 72.2% of patients progressed to death, this finding had no association with the immunohistochemical data. There was no statistically significant differences between the number of CD8 + and NK cells and the ability of tumor response to radiotherapy and chemotherapy, or with overall survival and relapse-free survival of patients. However, especially in relation to a learned response, we found that this group of patients with advanced disease have a low count of CD8 + T cells active. Believing in the role that the immune response plays in the local fight against neoplastic cells, however, our results do not support the use of quantitative analysis of CD8 + T cells and NK cells as a prognostic factors for oral squamous cell carcinoma and oropharynx / A neoplasia maligna mais frequente da cavidade oral e da orofaringe ? o carcinoma epiderm?ide. Les?es com o mesmo estadiamento e submetidas ao mesmo protocolo terap?utico apresentam, por vezes, cursos evolutivos diferentes. O escopo do presente trabalho foi investigar, atrav?s de um coorte retrospectivo, associa??es entre a quantidade de c?lulas TCD8+ e natural killer, identificadas imuno-histoquimicamente no infiltrado inflamat?rio de uma s?rie de casos de carcinoma epiderm?ide oral e orofaringeano, e o n?vel de resposta tumoral ao tratamento radioter?pico e quimioter?pico, a sobrevida global e sobrevida livre de recidiva dos pacientes. Foram identificados 54 pacientes com doen?a irressec?vel, tratados exclusivamente com radioterapia e quimioterapia. A mediana de seguimento foi de 22 meses. A amostra se caracterizou pelo predom?nio de indiv?duos masculinos, com idade mediana de 60 anos; todos eram tabagistas. O s?tio mais frequente foi a l?ngua oral e 81,5% encontravam-se no est?dio IV. Os pacientes com doen?a na cavidade oral tiveram uma pior resposta ao tratamento (p=0,006), pior sobrevida livre de recidiva (p=0,007), pior sobrevida global (p=0,007). O est?dio T avan?ado se demonstrou um fator progn?stico negativo (p=0,006) para a resposta ao tratamento cl?nico efetuado. Foi realizada imuno-histoqu?mica para marcar c?lulas CD8+ (anti-CD8) e c?lulas NK (anti-CD57). Os linf?citos positivos e negativos para as marca??es foram contados atrav?s do programa ImageJ?. Dois grupos foram criados para cada marca??o avaliada: Grupo I: pacientes com mais de 50% das c?lulas positivas; Grupo II: menos de 50% das c?lulas marcadas. Para as c?lulas CD8+ detectamos que 38 (70,3%) eram do Grupo I CD8+ e 16 (29,7%) do Grupo II CD8+. Para as c?lulas NK, 26 (48,15%) Grupo I NK e 28 (51,85%) Grupo II NK. Em rela??o ? resposta cl?nica ao tratamento, observamos que 39% dos pacientes obtiveram resposta completa e 25,9% permaneceram sem recidiva ao final do seguimento. Esses resultados foram melhores no Grupo I CD8+ (p=0,2). Identificamos que 72,2% dos pacientes evolu?ram para o ?bito, esse achado n?o teve associa??o com os dados imuno-histoqu?micos. N?o se observou diferen?as estatisticamente significantes entre a quantidade de c?lulas CD8+ e NK e a capacidade de resposta tumoral ao tratamento radioter?pico e quimioter?pico, nem com a sobrevida global e sobrevida livre de recidiva dos pacientes. Contudo, principalmente em rela??o a resposta adquirida, detectamos que este grupo de pacientes com doen?a avan?ada tem uma baixa contagem de c?lulas TCD8+ ativas. Acreditando no papel fundamental que a resposta imune exerce no combate local ?s c?lulas neopl?sicas; no entanto, nossos resultados n?o suportam a utiliza??o da an?lise quantitativa das c?lulas TCD8+ e NK como um dos fatores progn?sticos para o carcinoma epiderm?ide oral e de orofaringe

Made available in DSpace on 2014-12-17T15:32:22Z (GMT). No. of bitstreams: 1 KaruzaMAP.pdf: 544780 bytes, checksum: e0fadeed7d2d1ec7568970935306d05c (MD5) Previous issue date: 2006-02-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The Human Papillomavirus (HPV) has been strongly implicated on development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved on such mechanism of defense detaches the Langerhans cells (LC), which are responsible for processing and presenting antigens. The purpose of this study was to evaluate the immunohistochemical reactivity for Langerhans cells between HPV positive and HPV negative OSCC, as well as, the relation of the immunoreactivity for this cells and the histological grading of malignancy proposed by Bryne (1998) and modified by Miranda (2002). Additionally, HPV infection was evaluated in relation to sex, age, lesion localization and histological grading of malignancy. In the total, 27 cases of OSSC were evaluated, 09 of them HPV positive and 18 HPV negative. Anti S-100 antibody was utilized for the immunohistochemical labelling, followed by the counting of LCs in 5 highpower fields (400x). No statistically significant difference was verified between the variables sex, age, lesion localization, histological grading of malignancy and HPV presence in OSSC. There was neither association between the immunohistochemical labeling for LCs (S-100+) and HPV infection nor correlation between the quantity of LCs labeled and the histological grading of malignancy of OSSC. The results suggest that despite the absence of statistically significant difference, the presence of HPV in such cases of OSCC can alter the immunological system, particularly the Langerhans cells / O Papilomav?rus Humano (HPV) tem sido implicado fortemente no desenvolvimento de alguns carcinomas epiderm?ides orais (CEOs). Contudo, o sistema imunol?gico reage de alguma forma ? presen?a desse v?rus. Dentre as c?lulas envolvidas nesse mecanismo de defesa, destaca-se a c?lula de Langerhans (CL), por serem c?lulas processadoras e apresentadoras de ant?genos. O objetivo desse estudo foi avaliar a marca??o imuno-histoqu?mica das c?lulas de Langerhans entre os casos de CEOs HPV positivos e negativos, bem como a rela??o da imunomarca??o dessas c?lulas e a grada??o histol?gica de malignidade proposta por Bryne (1998) e modificada por Miranda (2002). Adicionalmente, a infec??o pelo HPV foi estudada com rela??o ao sexo, idade, localiza??o da les?o e a grada??o histol?gica de malignidade. Foram analisados 27 casos de CEOs, sendo 09 destes HPV positivos e 18 casos negativos. Para a marca??o imuno-histoqu?mica utilizou-se o anticorpo anti S-100, sendo as CLs quantificadas em 5 campos de maior aumento (400x). A an?lise estat?stica revelou n?o existir rela??o das vari?veis, sexo, idade, localiza??o da les?o e grada??o histol?gica, com a presen?a do HPV nos CEOs estudados. N?o existiu associa??o entre a marca??o imuno-histoqu?mica das CLs(S-100+) e a infec??o pelo HPV, e tamb?m n?o houve correla??o entre as CLs imunomarcadas e a grada??o histol?gica nos casos de CEOs analisados. Diante desses resultados, pode-se sugerir que mesmo n?o havendo diferen?a significativa, a presen?a do HPV nos casos de carcinoma epiderm?ide oral pode alterar o sistema imune, particularmente as c?lulas de Langerhans

Made available in DSpace on 2014-12-17T15:32:24Z (GMT). No. of bitstreams: 1 JoaoAVGF.pdf: 1413564 bytes, checksum: f5d8ea2da8907cd551169a4091430007 (MD5) Previous issue date: 2006-02-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity, accounting for more than 90% of all malignancies in this location. Cyclooxygenases (COX s) are key enzymes on arachidonic acid metabolism and prostaglandin synthesis, being expressed basically in two forms: the constitutive (COX-1) and the inducible (COX-2). Increased levels on the expression of COX-2 have been implicated in the pathogenesis tumor progression of various forms of human cancer, including oral squamous cell carcinoma, some of what suggesting a possible interaction between COX-2 and the protein expressed by the tumor suppressor gene p53, mutated in more than 50% of all human cancers. The mean of the present research consisted in analyze the correlation between the expression of COX-2 and p53, at the protein level, as well as evaluate the difference on the expression of these two proteins with the histological grading of malignancy. 34 cases of oral squamous cell carcinoma were selected and graded according to the histological grading system proposed by Bryne (1998) and the labeling indexes (LI s) for COX-2 and p53 evaluated using immunohistochemistry method. The results revealed that COX-2 was expressed in increased levels in most of the specimens, although there was no statistic significant correlation between LI s from COX-2 and p53 (p>0.05), and there were no statistical differences on the expression of these proteins between tumors of high and low grade of malignancy (p>0.05). Interestingly, the expression of COX-2 and p53 was detected in fragments of dysplastic oral epithelium adjacent to tumor areas, on basal and suprabasal layers. The absence of statistical correlation between the expression of COX-2 and p53 proteins do not rule ot the existence of a relation between them, were it may reflect the diversity of regulatory pathways between both, different direct and indirect inhibitory effects of COX-2 over p53, as well as the wide range of activation macheenisms for COX-2 and mutational status of the p53 gene Another conclusion point that the increased expression of COX-2 observed in oral squamous cell carcinomas suggest a role for this protein in the processes of pathogenesis and tumoral evolution of this malignant neoplasm / O carcinoma epiderm?ide ? a neoplasia maligna mais comum na cavidade oral, representando mais de 90% das malignidades nesta localiza??o. As cicloxigenases (COX s) s?o enzimas chave no metabolismo do ?cido aracd?nico e s?ntese de prostaglandinas, sendo expressas basicamente sob duas formas: uma constitutiva (COX-1) e uma induzida (COX-2). N?veis elevados na express?o da COX-2 t?m sido implicados na patog?nese e progress?o tumoral em diversos tipos de c?ncer em humanos, incluindo o carcinoma epiderm?ide oral, alguns dos quais sugerindo uma poss?vel intera??o entre a COX-2 e a prote?na expressa pelo gene supressor tumoral p53, mutado em mais de 50% de todos c?nceres humanos. O prop?sito da presente pesquisa consistiu em analisar a correla??o entre a express?o de COX-2 e p53, em n?vel de prote?na, bem como avaliar a diferen?a na express?o destas duas prote?nas em rela??o ao grau histol?gico de malignidade. Para tal, foram selecionados 34 casos de carcinoma epiderm?ide oral, os quais foram classificados de acordo com o sistema de grada??o histol?gica de malignidade proposto por Bryne (1998) e cujos ?ndices de positividade para COX-2 e p53 foram avaliados atrav?s da t?cnica imuno-histoqu?mica. O resultados revelaram que a COX-2 esteve expressa em n?veis elevados na maior parte dos esp?cimes analisados, embora n?o se tenha verificado correla??o estatisticamente significativa entre os IP s da COX-2 e da p53 (p>0,05), tampouco diferen?a estatisticamente significativa entre a express?o destas prote?nas entre tumores de alto e baixo grau de malignidade (p>0,05). Interessantemente, foi detectada a express?o da COX-2 e da p53 em fragmentos de epit?lio oral displ?sico, nas camadas basal e parabasal, adjacentes ao tumor. A aus?ncia de correla??o estat?stica entre a express?o das prote?nas COX-2 e p53 n?o descarta a exist?ncia de uma rela??o entre as mesmas, podendo refletir a diversidade de vias regulat?rias entre ambas, os diferentes efeitos inibit?rios diretos e indiretos da COX-2 sobre a p53, bem como os in?meros mecanismos de ativa??o da COX-2 e o estado mutacional do gene p53. Conclui-se ainda que a elevada express?o da COX-2 observada em carcinomas epiderm?ides orais sugere um papel desta prote?na dentro dos processos de patog?nese e evolu??o tumoral desta neoplasia maligna

Made available in DSpace on 2014-12-17T15:32:25Z (GMT). No. of bitstreams: 1 AndreaFS_tese.pdf: 610478 bytes, checksum: 22934e3fba7a401686d3b0057e0e7f35 (MD5) Previous issue date: 2007-07-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The expression of bone morphogenetic proteins (BMPs) is altered in a variety of human canceres. The BMP-2/4 and BMPR-IA were recently shown to be overexpressed in high-risk premalignant and malignant lesions of oral epithelium. The present study analysed the expression of BMP-2/4 and BMPR-IA in Oral Squamous Cell Carcinoma (OSCC) such as their implications in disease prognostic using munohistochemistry. Ten cases of Oral Fibroepithelial Hiperplasia were selected as a control group. The experimental group included 16 cases of OSCC without metastases and 7 cases of OSCC metastatic. The presence or absence of nodal metastases was used as parameter to evaluated the disease prognostic. The results demonstrated weak immunoreactivity for BMP-2/4 and BMPR-IA in every case of the control group. In the cases of OSCC with metastases an overexpression of BMP-2/4 (71,4%) was observed while the BMPR-IA showed weak expression (85,7%). In the cases of OSCC without metastases BMP-2/4 (62,5%) and BMPR-IA showed strong immunostaining standing out an overexpression of the receptor in all the specimens. Observed statistical significance for correlation between the oral cancer prognostic and the staining intensity of the BMP-2/4 (p=0,002). There wasn t statistical significance for association between the staining intensity of the BMPR-IA and the disease prognostic (p<0,001). In conclusion, this findings suggest that the overexpression of BMP-2/4 associated with the loss of expression of the BMPR-IA in OSCC metastatic has prognostic relevance, as the loss of sensitivity to BMPs can be an indicative of metastases development in OSCC / A express?o das prote?nas morfogen?ticas ?sseas (BMPs) est? alterada em v?rios c?nceres humanos. A BMP-2/4 e o BMPR-IA foram recentemente encontrados superexpressos em les?es malignas e pr?-malignas de alto risco em epit?lio oral. Este estudo analisou a express?o da BMP-2/4 e seu receptor BMPR-IA em 23 esp?cimes de Carcinoma Epiderm?ide Oral (CEO), utilizando a imuno-histoqu?mica. O grupo controle constou de 10 casos de Hiperplasia Fibro-epitelial da mucosa oral. O grupo experimental foi constitu?do por 16 casos de CEO n?o metast?tico e 7 casos de CEO metast?tico. Utilizou-se o par?metro presen?a ou aus?ncia de met?stase nodal para avaliar o progn?stico da doen?a. Os resultados demonstraram imunorreatividade fraca para a BMP-2/4 e o BMPR-IA em todos os esp?cimes do grupo controle. No grupo experimental com met?stase, a BMP-2/4 exibiu forte expressividade (71,4%), enquanto que o BMPR-IA mostrou fraca express?o (85,7%). No grupo experimental sem met?stase, evidenciou-se forte express?o para a BMP-2/4 (62,5%) e para o BMPR-IA (100%). Encontrou-se signific?ncia estat?stica para a associa??o entre o progn?stico do CEO e a intensidade de marca??o da BMP-2/4 (p=0,002). Para o BMPR-IA n?o houve signific?ncia estat?stica ? sua associa??o com o progn?stico da doen?a (p<0,001), em fun??o do tamanho da amostra. Portanto, os resultados sugerem que a fraca expressividade do BMPR-IA associada ? forte express?o da BMP-2/4, no grupo experimental com met?stase, tem relev?ncia progn?stica, j? que a perda de sensibilidade ?s BMPs, atrav?s da perda de express?o de seus receptores pode ser indicativo de desenvolvimento de met?stase em CEO

Made available in DSpace on 2014-12-17T15:32:28Z (GMT). No. of bitstreams: 1 MartaRP.pdf: 1904281 bytes, checksum: 2912c6b8ea9a773c553d0776245f93a5 (MD5) Previous issue date: 2009-02-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Oral Epithelial Dysplasia (OED) is the lesion that precedes or co-exists with the Oral Squamous Cell Carcinoma (OSCC), presenting molecular and/or histological similar alterations. The divergences about the malignization potential of OEDs and the role of inflammation in this process make hard the early diagnosis and evaluation of OSCCs aggressiveness. Thus, it became the goal of this study to evaluate the role of inflammation in oral carcinogenesis and tumoral aggressiveness. For this purpose a morphological study was performed in 20 OED cases and 40 OSCC cases to detect the malignization potential of OEDs and the histologic malignancy grading (HMG) of OSCCs, analyzing superficial masses for dismorphism evaluation and the invasive front for evaluation of tumoral growing; and immunohistochemical, using anti-CD8, anti-FOXP3, anti-TGF?, anti-TNF? and anti-NF-?B antibodies, comparing their with the types lesion, histological degree and intensity of the inflammatory infiltrate. The results were statistically significant for the parameters: cell maturity (p=0,0001), masses presence (p=0,038) and dismorphism (p=0,037), when associated to HMG. To compare the expression of the markers with the types lesion, a significantly higher expression of CD8 (p=0,001) and NF-?B (p=0,002) in the OED, and also a smaller expression of the epithelial TGF? in the severe OEDs (p=0,011), without significant expression between OSCC degrees. By relating the expression of the studied markers with the inflammatory infiltrate intensity, a positive relation was observed with: inflammatory TNF?(p=0,003), epithelial TNF? and NF-?B (p=0,051 and p=0,004), in OEDs; and with CD8 (p=0,021) and TNF? (p=0,015) in conjunctive OSCCs; and a negative relation with epithelial TNF? (p=0,034) in OSCCs. No significant relation was found between FOXP3 with any of the studied variables. These findings lead to the conclusion that, the study of the invasive front is as important as the study of superficial masses for the evaluation of tumoral aggressiveness; the intensity of the inflammatory infiltrate has no use as a parameter for prognostic evaluation of OSCC in routine exams, but, the molecular events detected in this study may be necessary to give basis for determining the malignant potential in OEDs and aggressiveness in OSCCs / A Displasia Epitelial Oral (DEO) ? a les?o que precede ou co-existe com o Carcinoma Epiderm?ide Oral (CEO), apresentando altera??es moleculares e/ou histol?gicas semelhantes. As diverg?ncias sobre o potencial de maligniza??o das DEO e o papel da inflama??o nestes processos t?m dificultado o diagn?stico precoce e a avalia??o da agressividade dos CEO. Sendo assim, tornou-se objetivo deste estudo avaliar o papel da inflama??o na carcinog?nese oral e agressividade tumoral. Para isso foi realizado estudo morfol?gico em 20 casos de DEO e 40 casos de CEO para detectar o potencial de maligniza??o das DEO e o Grau Histol?gico de Malignidade (GHM) dos CEO, analisando as massas superficiais para avalia??o do dismorfismo e o front invasivo para avalia??o do crescimento tumoral; e imuno-histoqu?mico, utilizando os anticorpos anti-CD8, anti-FOXP3, anti-TGF?, anti-TNF-? e anti-NF-?B, para comparar a express?o dos mesmos com o tipo de les?o, grau histol?gico e intensidade do infiltrado inflamat?rio. Os resultados foram estatisticamente significantes para os par?metros, maturidade celular (p=0,0001), presen?a de massas (p=0,038) e dismorfismo (p=0,037), quando associados aos GHM. Ao comparar a express?o dos marcadores com o tipo de les?o, encontrou-se uma express?o significativamente maior do CD8 (p=0,001) e do NF-?B (p=0,002) nas DEO, assim como uma menor express?o do TGF? epitelial nas DEO severas (p=0,011), n?o tendo express?o significativa entre os graus dos CEO. Ao relacionar a express?o dos marcadores estudados com a intensidade do infiltrado inflamat?rio, observou-se uma rela??o positiva com o TNF? inflamat?rio (p=0,003), o TNF? e o NF-?B epiteliais (p=0,051 e p=0,004), nas DEO; com o CD8 (p=0,021) e o TNF? (p=0,015) no conjuntivo dos CEO; e uma rela??o negativa com o TNF? (p=0,034) epitelial dos CEO. N?o foi encontrada rela??o significativa da FOXP3 com nenhuma das vari?veis estudadas. Esses achados levaram a concluir que, o estudo do front invasivo ? t?o importante quanto o estudo das massas superficiais para avalia??o da agressividade tumoral; a intensidade do infiltrado inflamat?rio n?o pode ser utilizado como par?metro para avalia??o progn?stica do CEO no exame de rotina; mas os eventos moleculares detectados neste estudo podem ser necess?rios para embasar a determina??o do potencial de malignidade nas DEO e da agressividade nos CEO