Diante dos nossos resultados, podemos concluir que:
1. A expressão imuno-histoquímica do complexo E-caderina/β-catenina foi maior, de forma estatisticamente significativa, em carcinomas adenóides císticos que nos adenomas pleomórficos, assim como, dentro dos adenomas pleomórficos foi ausente ou focal nas áreas estromais, levando-se sugerir que a expressão destas proteínas está relacionada com a diferenciação do componente mioepitelial das neoplasias.
2. Quando os subtipos histológicos do carcinoma adenóide cístico foram comparados em relação ao padrão de marcação imuno-histoquímica de E- caderina/β-catenina não houve diferença estatisticamente significativa. Tal fato em associação a imuno-marcação reduzida observada em adenomas pleomórficos – neoplasia benigna – indica que a expressão deste complexo protéico não parece estar relacionada com o comportamento biológico deste tumor maligno.
3. A redução na marcação imuno-histoquímica da E-caderina nos casos polimórficos em relação aos casos sem polimorfismo, embora não tenha sido estatisticamente significativa, sugere que, em parte, a expressão gênica da E- caderina está diminuída nestes casos.
4. A semelhança no padrão de expressão imuno-histoquímica de β-catenina entre os grupos com e sem variação na mobilidade eletroforética em PCR- SSCP indica que possíveis mutações do gene CTNNB1 sugeridos nesta amostra não alteram a expressão protéica.
SUMMARY
Alterations of E-cadherin and β-catenin genes in pleomorphic adenoma and adenoid cystic carcinoma: molecular and immunohistochemical study
Pleomorphic adenoma and adenoid cystic carcinoma represent a benign and malignant salivary gland neoplasm, respectively, that shares the same histological origin, however with distinct biological behavior. The aim of the present study was identify the -160 C/A polymorphism in the gene CDH1, mutational analysis of CTNNB1 gene and evaluation the expression of the E-cadherin and β-catenin in pleomorphic adenomas and adenoid cystic carcinomas. Furthermore, it was proposed correlate the immunochemistry staining patterns with the polymorphism and mutations. Twenty-four pleomorphic adenomas and 24 adenoid cystic carcinomas were retrieved. The polymorphism analysis was performed by restriction fragment length polymorphism (RFLP), using the restriction enzymes HphI or AflIII and the mutational screening was performed by PCR-single strand conformational polymorphism (PCR-SSCP). The immunohistochemical analysis was taken by the counting of cells, recorded as the Hscore index, and considering the presence or absence, intensity, distribution and localization of proteins expression. Comparing the two neoplasms, the results demonstrated statistically significant difference for the E-cadherin and β-catenin expression, with pleomorphic adenoma presenting weaker immunostaining. Was observed statistical correlation between E-cadherin and β-catenin expression. CDH1 heterozigotic polymorphism was seen in two cases and 13 cases displayed abnormal mobility electrophoretic shifts, suggesting CTNNB1 gene mutation. The immunohistochemical expression was not statistically correlated with the polymorphism or suggested mutations. In conclusion this study supports that the E-cadherin/β-catenin complex immunohistochemical expression might be related with the myoepithelial component amount and differentiation neither the tumor biological behavior. The cases that showed E-cadherin gene polymorphism presented reduced protein expression and, moreover, CTNNB1 suggested mutations seem not influence in the β-catenin protein expression.
Key-words: Pleomorphic adenoma, adenoid cystic carcinoma, E-cadherin, β-catenin, RFLP, SSCP.
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