Made available in DSpace on 2014-12-17T15:32:19Z (GMT). No. of bitstreams: 1 DmitryJSS_DISSERT.pdf: 3987707 bytes, checksum: acff9df3451c8d6fc62a6e590d027fca (MD5) Previous issue date: 2011-12-09 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 &#956;m were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip / O carcinoma epiderm?ide (CE) de l?bio inferior evolui, em 95% dos casos, de uma condi??o potencialmente maligna denominada queilite act?nica (QA). Ambas les?es s?o causadas principalmente pela exposi??o cr?nica ao componente ultravioleta da radia??o solar, especialmente o subtipo UVB. Esta exposi??o pode causar altera??es no ciclo celular e danos aos sistemas de reparo do DNA, como o mismatch repair, conduzindo a altera??es em prote?nas de reparo, como hMLH1 e hMSH2. Esta pesquisa objetivou investigar a express?o imunoistoqu?mica das prote?nas hMLH1 e hMSH2 em CEs de l?bio inferior e QAs com graus variados de displasia epitelial e desse modo tentar fornecer informa??es adicionais sobre a carcinog?nese de l?bio inferior. A amostra foi composta por 40 casos de QAs e 40 casos de CEs de l?bio inferior. Cortes histol?gicos de 3 &#956;m foram submetidos ao m?todo da imunoperoxidase, para a an?lise imunoistoqu?mica das les?es foram contadas 1000 c?lulas (positivas e negativas), os dados foram avaliados tanto em n?meros absolutos quanto em percentual de c?lulas imunomarcadas, este ?ltimo atrav?s da atribui??o de escores. Para as associa??es e compara??es das m?dias e escores da imunoexpress?o das prote?nas foram utilizados os testes estat?sticos Qui-quadrado de Pearson, Exato de Fisher, t student, ANOVA one-way, Mann-Whitney e Kruskal-Wallis. O n?vel de signific?ncia adotado foi de 5%. Verificou-se que, em CEs de l?bio inferior, as m?dias das prote?nas foram maiores em pacientes do sexo feminino (hMLH1 369,80 + 223,98 =; hMHS2 = 534,80+343,62), com menos de 50 anos (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) e que foram classificados como de baixo grau de malignidade (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), apenas a vari?vel sexo (prote?na hMLH1) apresentou signific?ncia estat?stica (p=0,034). Ao comparar as diferentes les?es, observou-se que em ambas prote?nas, a m?dia das c?lulas epiteliais positivas diminuiu conforme a les?o era gradada em est?gios mais avan?ados. As QAs classificadas sem displasia ou com displasia epitelial leve apresentaram a maior m?dia de c?lulas imunomarcadas (hMLH1 = 721,23 + 88,116; hMHS2 = 781,50 + 156,93). As QAs gradadas como displasia epitelial moderada ou severa apresentaram valores intermedi?rios (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) e os CEs de l?bio inferior apresentaram as menores m?dias (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68), observou-se diferen?a estat?stica significante entre os grupos (p<0.001). Em conclus?o, os dados deste estudo sustentam a hip?tese de que altera??es na imunoexpress?o destas prote?nas est?o relacionadas ao processo de carcinog?nese de l?bio inferior