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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Estudo da associaÃÃo entre a acromegalia e a presenÃa da mutaÃÃo BRAFV600E e a expressÃo imunohistoquÃmica de IGF-1 e galectina-3 no carcinoma papilÃfero de tireoide. / Study of the association between acromegaly and the presence of BRAFV600E mutation and immunohistochemical expression of IGF-1 and galectin-3 in papillary thyroid carcinoma.

Renan MagalhÃes Montenegro 31 August 2012 (has links)
nÃo hà / INTRODUÃÃO: Estudos epidemiolÃgicos sugerem que o carcinoma de tireoide seja a neoplasia maligna mais frequente nos pacientes acromegÃlicos. Atà este momento nÃo hà relatos de estudos avaliando marcadores moleculares do carcinoma papilÃfero de tireoide (CPT) nessa populaÃÃo. OBJETIVOS: Avaliar a associaÃÃo entre acromegalia, presenÃa da mutaÃÃo BRAFV600E, marcadores imunohistoquÃmicos (galectina-3 e IGF-1) e caracterÃsticas clÃnico-patolÃgicas em pacientes acromegÃlicos com CPT. MATERIAL E MÃTODOS: Trata-se de um estudo transversal realizado no perÃodo de janeiro/09 a dezembro/2011, onde 11 pacientes acromegÃlicos com CPT, provenientes de 5 centros brasileiros de referÃncia no tratamento da acromegalia foram comparados com 45 pacientes com CPT sem acromegalia. Foram estudadas variÃveis clÃnicas e histopatolÃgicas do CPT. Utilizou-se cortes histolÃgicos de CPT emblocados em parafina para o estudo da mutaÃÃo BRAFV600E e para a anÃlise imunohistoquÃmica dos marcadores IGF-1 e galectina-3. Na anÃlise utilizou-se os testes t de student e do qui-quadrado (software SPSS, versÃo 13.0 para Windows) (p<0,05). RESULTADOS: A idade mÃdia dos pacientes acromegÃlicos com CPT foi de 61,5  6,02 anos, sendo 72,7% do sexo feminino. O tempo mÃdio de diagnÃstico da acromegalia foi de 7,7  3,90 anos, sendo o intervalo entre o diagnÃstico da acromegalia e do CPT, em mÃdia, 3,4  2,71 anos. Os nÃveis sÃricos de IGF-1 dos acromegÃlicos ao diagnÃstico do CPT foi de 417,0 ng/mL. NÃo houve diferenÃa quanto ao estadiamento TNM (Tumor, Nodule, Metastasis) e Ãndice prognÃstico AMES (Ages, Metastasis, Extent, Size) entre os grupos. Houve maior prevalÃncia da mutaÃÃo BRAFV600E (90,9% vs 55,6%; p=0,039) e de forte imunoexpressÃo para IGF-1 (88,9% vs 38,1%; p= 0,017) nos acromegÃlicos. NÃo houve diferenÃa na expressÃo de galectina-3 entre os grupos. CONCLUSÃO: Neste trabalho, pela primeira vez se mostrou uma alta prevalÃncia da mutaÃÃo BRAFV600E em CPT de acromegÃlicos, muito superior à descrita na populaÃÃo com CPT neste e em estudos anteriores (cerca de 40%). Contudo essa mutaÃÃo nÃo se mostrou associada a um fenÃtipo mais agressivo do tumor, o que diverge dos achados em populaÃÃo nÃo acromegÃlica com CPT. Conclui-se que a acromegalia à possivelmente associada à mutaÃÃo BRAFV600E em pacientes acromegÃlicos com CPT. Novos estudos serÃo necessÃrios para definir os mecanismos responsÃveis por tal associaÃÃo. / INTRODUCTION: Epidemiological studies suggest that thyroid carcinoma is the most common malignant neoplasm in acromegalic patients. At this moment there are no reports of studies evaluating molecular markers of papillary thyroid carcinoma (PTC) in this population. OBJECTIVES: The present work aimed to evaluate the association between acromegaly, expression of the mutation BRAFV600E, immunohistochemical markers (galectin-3 and IGF-1), and clinical-pathological characteristics in acromegalic patients with PTC. MATERIALS AND METHODS: This is a cross-sectional study conducted from January/09 to December/2011, where 11 acromegalic patients with CPT, from 5 Brazilian centers of reference in the treatment of acromegaly were compared with 45 patients with acromegaly without PTC. We evaluated clinical and histopathological variables of PTC. We used histological PTC embedded in paraffin for mutation study BRAFV600E and immunohistochemical analysis of markers IGF-1 and galectin-3. In the analysis we used the Student t test and chi-square test (SPSS software, version 13.0 for Windows) (p <0.05). RESULTS: The average age of acromegalic patients with PTC was 61.5  6.02 years and 72.7% were female. The average time of diagnosis of acromegaly was 7.7  3.90 years, and the interval between diagnosis of acromegaly and PTC was an average 3.4  2.71 years. The serum levels of IGF-1 in the diagnosis of acromegaly PTC was 417.0 ng / mL. There was no difference in the TNM (Tumor, Nodule, Metastasis) and AMES prognostic index (Ages, Metastasis, Extent, Size) between groups. There was a higher prevalence of the BRAFV600E mutation (90.9% vs 55.6%, p = 0.039) and stronger immunohistochemical expression for IGF-1 (88.9% vs 38.1%, p = 0.017) in acromegaly. There was no difference in the expression of galectin-3 between the groups. CONCLUSION: This work for the first time showed a high prevalence of mutations in BRAFV600E in PTC of acromegalic patients superior to those described in the population with PTC in this and previous studies (approximately 40%). However, this mutation was not associated with a more aggressive tumor phenotype, which differs from the findings in acromegalic population without PTC. We conclude that acromegaly is possibly associated to a mutation BRAFV600E in acromegalic patients with CPT. Further studies are needed to define the mechanisms responsible for this association.

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