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Express?o imuno-histoqu?mica do ativador de plasminog?nio do tipo uroquinase e seu receptor em carcinoma epidermoide de l?ngua oral e sua rela??o com par?metros cl?nico-patol?gicosSerpa, Marianna Sampaio 12 February 2016 (has links)
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Previous issue date: 2016-02-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O carcinoma epidermoide oral (CEO) ? a neoplasia maligna mais comum da cavidade oral, apresentando uma alta taxa de mortalidade. Devido a isto, a descoberta de biomarcadores que facilitem a compreens?o do comportamento biol?gico desse tumor e aprimorem o tratamento ? necess?rio. O ativador de plasminog?nio do tipo uroquinase (uPA) e o seu receptor, uPAR, t?m se destacado por atuarem na prote?lise de estruturas da membrana basal e matriz extracelular, facilitando a invas?o tumoral. O presente estudo se prop?s a avaliar a imunoexpress?o dessas prote?nas em 46 casos de carcinoma epidermoide de l?ngua oral (CELO). Esses resultados foram relacionados com a presen?a de met?stase, estadiamento cl?nico TNM, recidiva locoregional, desfecho da les?o e grada??o histol?gica de malignidade. A imunomarca??o de cada caso foi avaliada semiquantitativamente, tanto no front de invas?o como no centro do tumor, na qual foram atribu?dos os escores: 0 (0% de c?lulas positivas), 1(1-10% de c?lulas positivas), 2 (11-50% de c?lulas positivas), 3 (mais de 50% de c?lulas positivas). A express?o do uPA foi observada em 93,5% dos casos no front de invas?o, com predom?nio do escore 2 (34,8%), e em 67,9% dos casos no centro do tumor, com predom?nio do escore 1 (32,6%). De modo geral, os par?metros cl?nicos n?o exerceram influ?ncia na imunoexpress?o do uPA. Em rela??o ? grada??o histol?gica, foi observada uma maior express?o de uPA nos casos de alto grau de malignidade em rela??o aos de baixo grau de malignidade (p=0,05). Quando analisado em rela??o aos par?metros morfol?gicos, foi identificado uma maior express?o do uPA nos casos de pior padr?o de invas?o (p=0,03). A express?o do uPAR foi observada em 73,9% dos casos no front de invas?o, com predom?nio do escore 1 (45,65%), e em 47,5% dos casos no centro do tumor, com predom?nio do escore 0 (54,35%). Embora n?o tenham sido observadas signific?ncias estat?sticas em rela??o ? met?stase linfonodal, estadiamento cl?nico TNM, desfecho e grada??o histol?gica, houve uma maior express?o do uPAR nos casos com recidiva locoregional em rela??o aos sem recidiva (p=0,04). Em rela??o ? an?lise da localiza??o tumoral, foi observada uma maior express?o de uPA e uPAR no front de invas?o em rela??o ao centro do tumor (p<0,001). Na correla??o entre uPA e uPAR, n?o foi observada signific?ncia estat?stica. Com base nestes resultados, sugere-se que o uPA e uPAR estejam envolvidos na progress?o do CELO, atuando principalmente na regi?o mais profunda do tumor. / Squamous cell carcinoma (SCC ) is the most common malignancy of the oral cavity (OSCC), with a high mortality rate. Due to this, the discovery of biomarkers that facilitate the understanding of the biological behavior of the tumor and improve treatment is necessary. Urokinase type plasminogen activator (uPA) and its receptor, uPAR, are responsible for the proteolysis of structures of the basement membrana and extracellular matrix, facilitating tumor invasion. This study aims to assess the immuno expression
of these proteins in 46 cases of squamous cell carcinoma of the oral tongue (OTSCC). These results were related to the presence of metastasis, clinical TNM staging, locoregional recurrence, outcome of the lesion
and histological grading. Immunostaining of each case was evaluated semiquantitatively, in the front of
invasion and center of the tumor, in which scores were assigned: 0 (0% of positive cells), 1 (1-10% of
positive cells), 2 (11 -50% positive cells) and 3 (more than 50% positive cells). The expression of uPA was observed in 93.5% (n=43) of the cases in the front of invasion, with predominance of score 2 (n=16; 34.8%) and in 67.9% (n=31) of the cases in the center of the tumor, with predominance of score 1 (n=15; 32.6%). Overall, the immunoexpression of uPA was not associated with clinical parameters. Regarding the malignant histological grading, a higher expression of uPA was observed in cases of high-grade malignancy comp ared to low-grade malignancy (p=0.05). Regarding the morphological parameters, increased expression of uPA was observed in the worst mode of invasion (p=0.03 ). The expression of uPAR was observed in 73.9% of cases in the front of invasion, with a predominance of score 1
(n=21; 45.6 %), and in 47.5% (n=21) of the cases in the center of the tumor, with a predominance of score 0 (n=25; 54.4%). Although no statistical differences were observed in relation to lymph node metastasis, clinical TNM staging, outcome, and histological grading, there was a higher expression of uPAR in cases with locoregional recurrence (p=0.04). Regarding the tumor intra -localization, it was observed an increased expression of uPA and uPAR at the front of invasion in relation to the center of the
tumor (p<0.001). Regarding the correlation between uPA and uPAR, there was no statistical sign ificance. Based on these results, it is suggested that uPA and uPAR are involved in the progression of CELO, mainly in the deeper region of the tumor.
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