Made available in DSpace on 2014-12-17T15:32:15Z (GMT). No. of bitstreams: 1 BetaniaFR.pdf: 636142 bytes, checksum: 6061eebe55028f4725bba3031ee70b7a (MD5) Previous issue date: 2008-02-26 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Ameloblastoma and adenomatoid odontogenic tumor are odontogenic tumors arising from the odontogenic epithelium with distinct clinical behavior. In attempt to comprehend the interaction between the odontogenic tumor cells and the extracellular matrix, the present work evaluated and compared the immunohistochemical expression of the matrix metalloproteinases-1 (MMP-1), -2 (MMP-2) and -9 (MMP-9) in 20 cases of ameloblastoma and 10 adenomatoid odontogenic tumor. MMP-1 exhibited exuberant expression in the parenchyma and in the stroma of both studied tumors, while the MMP-2 showed varied expression with about of 80% and 60% of the neoplastic cells exhibiting positivity in the ameloblastoma and adenomatoid odontogenic tumor, respectively. With relation to the MMP-2 expression by the mesenchymal cells, it was observed that 65% of the ameloblastoma and 80% of the adenomatoid odontogenic tumor were positive. The immunoreactivity of MMP-9 was detected in all studied cases, although its expression had occurred predominantely in less than 50% of the parenchyma cells of the ameloblastoma, while in about of 60% of the adenomatoid odontogenic tumor more than 50% of cells were positive. The mesenchymal cells were positive to MMP-9 in 65% of the ameloblastoma and in 80% of the adenomatoid odontogenic tumor, respectively. Statistically significant difference was observed to the MMP-1 expression with relation to MMP-2 and MMP-9 in the ameloblastoma (p < 0.001). It was not possible to perform statistical analysis to the cases of adenomatoid odontogenic tumor, however there was a tendency toward a differential expression of the MMP-1 with relation to other studied MMPs. These results suggest that MMP-1, - 2 and -9 are implicated in the growth and progression of both tumors analyzed as well as the more pronounced participation of the stroma in the ameloblastoma could together to be related to the higher clinical aggressiveness / O ameloblastoma e o tumor odontog?nico adenomat?ide s?o tumores odontog?nicos derivados do epit?lio odontog?nico que possuem comportamentos distintos. Na tentativa de compreender a intera??o existente entre as c?lulas tumorais e a matriz extracelular, o presente trabalho teve como objetivo avaliar e comparar a express?o das metaloproteinases-1 (MMP-1), -2 (MMP-2) e -9 (MMP-9), atrav?s da t?cnica imuno-histoqu?mica em 20 casos de ameloblastoma e 10 de tumor odontog?nico adenomat?ide. A MMP-1 teve uma marca??o predominante nos dois tumores, sendo observada tanto no par?nquima como no estroma de todos os tumores estudados. Para a MMP-2, observou-se uma express?o variada, sendo 80% e 60% das c?lulas tumorais imunorreativas nos ameloblastomas e tumores odontog?nicos adenomat?ides, respectivamente. Em rela??o ?s c?lulas do mes?nquima, 65% dos ameloblastomas e 80% tumores odontog?nicos adenomat?ides exibiram positividade. Verificou-se imunoexpress?o para a MMP-9 nas c?lulas parenquimatosas e estromais em todos os casos, sendo que nos ameloblastomas, houve o predom?nio de menos de 50% das c?lulas imunomarcadas; enquanto que em 60% dos tumores odontog?nicos adenomat?ides mais de 50% das c?lulas apresentaram positividade. Observou-se diferen?a estatisticamente significante na express?o da MMP-1 em rela??o ? MMP-2 e -9 nos ameloblastomas (p<0,001). A an?lise estat?stica n?o p?de ser aplicada para os tumores odontog?nicos adenomat?ides, por?m verificou-se tend?ncia de maior express?o da MMP-1 em rela??o ?s outras MMPs avaliadas. Os resultados deste estudo sugerem que as MMPs-1, -2 e -9 est?o relacionadas com crescimento e progress?o dos tumores analisados e, particularmente no ameloblastoma, sua maior agressividade pode resultar, em parte, pela participa??o tamb?m do estroma presente de forma bem mais marcante permeando o par?nquima tumoral e sendo fonte tamb?m das proteases estudadas

Made available in DSpace on 2014-12-17T15:32:22Z (GMT). No. of bitstreams: 1 MarceloABN_DISSERT.pdf: 4711000 bytes, checksum: ea3602bfcefe0d8448e9d402030634a2 (MD5) Previous issue date: 2014-02-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / BMPs are components superfamily ligands transformation growth fator-&#946; (TGF-&#946;) secreted into the extracellular environment, with mechanisms of intercellular communication through specific ligands and receptors in various target cells, being recognized for its influence in osteogenic induction, also play an important role in tissue homeostasis, cell proliferation, differentiation control , in addition to being present in the development of various malignancies. The aim of this study was to compare the immunohistochemical expression of BMP-2, BMP-4 and its receptors BMPRIA and BMPRII in cases of ameloblastoma and adenomatoid odontogenic tumor. The sample consisted of 20 cases of solid ameloblastoma (SA), 10 cases of ameloblastoma unicystic (UA) and 16 cases of adenomatoid odontogenic tumor (AOT). The expression of BMPs and their receptors was evaluated in the parenchyma and stroma of lesions, establishing the percentage of immunopositive cells (0 - negative; 1-1 % to 10 % of cells positive; 2 - 11% to 25% of positive cells; 3 - 26% to 50% of cells positive; 4 - 51% to 75 % of positive cells; 5 - more than 75% positive cells). Analysis of the expression of BMP-2 revealed no statistically significant differences in parenchymal (p = 0.925) and stromal component (p = 0.345) between the groups, as well as BMP-4 (p = 0.873 / p = 0.131). In the epithelial component, SA and AOT had a higher frequency of score 5. In turn, all cases of UA were classified as score 5. The analysis of the stromal component showed no statistically significant difference between groups with respect to median scores BMPRIA positivity (p = 0.768) and BMPRII (p = 0.779). In the epithelial component of SA and UA, no statistically significant correlations between imunoexpression proteins analyzed were observed. In turn, the group of AOT, statistically significant positive correlations between the scores of expression of all studied proteins were found. In the stromal component, statistically significant positive correlations were found only in the SA group in BMP -4 and BMPRII (r = 0.476; p = .034), in the UA in BMP-4 and BMPRIA (r = 0.709; p = 0.022). The results of this study suggest that the BMPs and their receptors are involved in the development process odontogenic tumors. BMP-4, in turn, besides being present in odontogenic tumors have the capacity to form mineralized material. / As BMPs s?o componentes da superfam?lia de ligantes do fator transformador de crescimento-&#946; (TGF-&#946;), secretados no meio extracelular, com mecanismos de comunica??o intercelular por meio de ligantes e receptores espec?ficos em diversas c?lulas-alvo, sendo reconhecidas por sua influ?ncia na indu??o osteog?nica, tamb?m desempenhando importante papel na homeostase tecidual, prolifera??o celular, no controle de diferencia??o, al?m de estar presente no desenvolvimento de diversas neoplasias. O objetivo deste estudo foi comparar a express?o imuno-histoqu?mica da BMP-2, BMP-4 e seus receptores BMPRIA e BMPRII em casos de Ameloblastoma e Tumor odontog?nico adenomat?ide. A amostra foi constitu?da de 20 casos de Ameloblastoma s?lido (AS), 10 casos de Ameloblastoma unic?stico (AU) e 16 casos de Tumor odontog?nico adenomat?ide (TOA). A express?o das BMPs e seus receptores foi avaliada no par?nquima e estroma das les?es, estabelecendo-se o percentual de c?lulas imunopositivas (0 negativo; 1 - 1% a 10% das c?lulas positivas; 2 - 11% a 25% das c?lulas positivas; 3 - 26% a 50% das c?lulas positivas; 4 - 51% a 75% das c?lulas positivas; 5 - mais 75% de c?lulas positivas). A an?lise da express?o de BMP-2 n?o revelou diferen?as estatisticamente significativas no componente par?nquimatoso (p = 0,925) e estromal (p = 0,345) entre as les?es estudadas, assim como a BMP-4 (p = 0,873 / p = 0,131). No par?nquima, o AS e TOA apresentaram maior frequ?ncia do escore 5. Por sua vez, todos os casos de AU foram classificados como escore 5. A an?lise do componente estromal revelou n?o haver diferen?a estatisticamente significativa entre os grupos em rela??o ?s medianas dos escores de positividade para BMPRIA (p = 0,768) e BMPRII (p = 0,779). No par?nquima do AS e do AU, n?o foram observadas correla??es estatisticamente significativas entre as imunoexpress?es das prote?nas analisadas. Por sua vez, no grupo dos TOAs, foram constatadas correla??es positivas, estatisticamente significativas, entre os escores de express?o de todas as prote?nas avaliadas. No componente estromal, foram constatadas correla??es positivas, estatisticamente significativas, apenas no grupo do AS em BMP-4 e BMPRII (r = 0,476; p = 0,034) e do AU em BMP-4 e BMPRIA (r = 0,709; p = 0,022). Os resultados do presente estudo sugerem que as BMPs e seus receptores est?o envolvidos no processo de desenvolvimento de tumores odontog?nicos. A BMP-4, por sua vez, al?m de estar presente em tumores odontog?nicos possui a capacidade de forma??o de material mineralizado

Made available in DSpace on 2015-03-03T15:38:43Z (GMT). No. of bitstreams: 1 PedroPAS_TESE_1-70.pdf: 4719637 bytes, checksum: 8f16cb0e2326a80cfc947b1ea2b89641 (MD5) Previous issue date: 2012-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Myofibroblasts are cells that exhibit a hybrid phenotype, sharing the morphological characteristics of fibroblasts and smooth muscle cells, which is acquired during a process called differentiation. These cells then start to express -SMA, a marker that can be used for their identification. Studies suggest that myofibroblasts are related to the aggressiveness of different tumors and that TGF-1 and IFN- play a role in myofibroblast differentiation, stimulating or inhibiting this differentiation, respectively. The objective of this study was to investigate the role of myofibroblasts in epithelial odontogenic tumors, correlating the presence of these cells with the aggressiveness of the tumor. Immunohistochemistry was used to evaluate the expression of TGF-1 and IFN- in myofibroblast differentiation, as well as the expression of MMP-13, which is activated by myofibroblasts, and of EMMPRIN (extracellular matrix metalloproteinase inducer) as a precursor of this MMP. The sample consisted of 20 solid ameloblastomas, 10 unicystic ameloblastomas, 20 odontogenic keratocysts, and 20 adenomatoid odontogenic tumors. For evaluation of myofibroblasts, anti- -SMA-immunoreactive cells were quantified in connective tissue close to the epithelium. Immunoexpression of TGF-1, IFN-, MMP-13 and EMMPRIN was evaluated in the epithelial and connective tissue components, attributing scores of 0 to 4. The results showed a higher concentration of myofibroblasts in solid ameloblastomas (mean of 30.55), followed by odontogenic keratocysts (22.50), unicystic ameloblastomas (20.80), and adenomatoid odontogenic tumors (19.15) (p=0.001). No significant correlation between TGF-1 and IFN- was observed during the process of myofibroblast differentiation. There was also no correlation between the quantity of myofibroblasts and MMP-13 expression. Significant correlations were found between MMP-13 and TGF-1 (r=0.087; p=0.011), between MMP- 13 and IFN- (r=0.348; p=0.003), as well as between EMMPRIN and MMP-13 (r=0.474; p<0.001) and between EMMPRIN and IFN- (r=0.393; p=0.001). The higher quantity of myofibroblasts observed in solid ameloblastomas, odontogenic keratocysts and unicystic ameloblastomas suggests that these cells are one of the factors responsible for the more aggressive biological behavior of these tumors, although the myofibroblast population was not correlated with TGF-1, IFN-, MMP-13 or EMMPRIN. The correlation between MMP- 13 and TGF-1 suggests that the latter induces the expression of this metalloproteinase. The present results also support the well-established role of EMMPRIN as an inducer of MMP-13. Furthermore, the relationship between EMMPRIN and IFN- and between MMP-13 and IFN- suggests synergism in the antifibrotic effect of these markers / Os miofibroblastos s?o c?lulas que apresentam um fen?tipo h?brido exibindo caracter?sticas morfol?gicas de fibroblastos e de c?lulas musculares lisas, sendo a aquisi??o de tal fen?tipo denominada diferencia??o, passando ent?o a expressar a -SMA, a qual ? importante na identifica??o dessas c?lulas. Estudos t?m sugerido que os miofibroblastos apresentam rela??o com a agressividade de diversas les?es e que o seu processo de diferencia??o estaria relacionado ? express?o do TGF- 1 e do IFN- atuando, respectivamente, no est?mulo e na inibi??o dessa diferencia??o. O objetivo deste trabalho foi investigar o papel dos miofibroblastos em les?es odontog?nicas epiteliais, relacionando-os ? agressividade das les?es e analisar por meio da imuno-histoqu?mica, a express?o do TGF- 1 e IFN- no processo de diferencia??o, al?m da an?lise da MMP-13 que ? ativada por miofibroblastos e do indutor de metaloproteinases de matriz (EMMPRIN) como precursor desta MMP. A amostra foi constitu?da por 20 ameloblastomas s?lidos, 10 ameloblastomas unic?sticos, 20 ceratocistos odontog?nicos e 20 tumores odontog?nicos adenomat?ides. Para a avalia??o dos miofibroblastos, foram quantificadas as c?lulas imunorreativas ao anticorpo - SMA presentes no tecido conjuntivo, pr?ximo ao tecido epitelial. As express?es de TGF- 1, IFN- , MMP-13 e EMMPRIN, foram avaliadas no componente epitelial e no conjuntivo, estabelecendo-se o percentual de imunorreatividade e atribuindo-se escores de 0 a 4. A an?lise dos miofibroblastos evidenciou maior concentra??o nos ameloblastomas s?lidos (m?dia de 30,55), seguido pelos ceratocistos odontog?nicos (22,50), ameloblastomas unic?sticos (20,80) e tumores odontog?nicos adenomat?ides (19,15) com valor de p= 0,001. N?o foi encontrada correla??o significativa entre TGF- 1 e IFN- no processo de diferencia??o dos miofibroblastos, bem como na rela??o entre a quantidade de miofibroblastos e a express?o da MMP-13. Constatou-se, correla??o estat?stica entre MMP-13 e TGF- 1 (r= 0,087; p= 0,011) al?m de significante correla??o entre MMP-13 e IFN- (r=0,348; p=0,003). Entre EMMPRIN e MMP-13 verificou-se signific?ncia (r= 0,474; p<0,001) assim como entre EMMPRIN e IFN- (r=0,393; p=0,001). A maior quantidade de miofibroblastos evidenciada nos ameloblastomas s?lidos, ceratocistos odontog?nicos e ameloblastomas unic?sticos sugere que estas c?lulas podem ser um dos fatores respons?veis para um comportamento biol?gico mais agressivo destas les?es, embora a popula??o de miofibroblastos n?o tenha apresentado correla??o com TGF- - 1, IFN- ,MMP-13 e EMMPRIN. Quanto a correla??o evidenciada entre MMP-13 e TGF- 1, isto pode sugerir um papel indutor do TGF- 1 para a express?o da MMP-13, assim como os resultados deste estudo refor?am a rela??o bem estabelecida do EMMPRIN como indutor da MMP-13. Constatou-se tamb?m rela??o entre EMMPRIN e IFN- assim como entre MMP-13 e IFN- sugerindo, dessa forma, um sinergismo na a??o anti-fibr?tica desses marcadores