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ALDH1L1 expression analysis in Hürthle cell tumors

Grant number: 15/19423-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Janete Maria Cerutti
Grantee:Nathalie Townsend Adelantado
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Epidemiological studies have shown that the prevalence of thyroid nodules in the adult population has increased considerably. About 4 to 7% of the adult population has a palpable nodule. However, with the use of high-resolution ultrasound, the prevalence can reach 67% of the population. Once identified a thyroid nodule, the main dilemma in nodule management is to exclude cancer. When a thyroid nodule is detected, a complete medical history, careful physical examination, laboratory and image tests will assist in the conduct and selection of nodes that must undergo fine-needle aspiration (FNA) for cytological diagnosis. Despites the fact that FNA has an excellent sensitivity and specificity in the diagnosis of thyroid nodules, due to the cytological similarity between benign (HCA and FTA) and malignant lesions (HCC and FTC) and the difficulty of detecting the presence of capsular or vascular invasion, 30 % of the nodules are classified as indeterminate. Patients with indeterminate diagnosis are referred for surgery for a more accurate diagnosis and appropriate treatment. Thus, several groups have sought molecular markers that could help in thyroid nodules preoperative diagnosis, especially in nodules classified as indeterminate in FNA. Our group identified by the SAGE technique 18 transcripts that showed expression in HCA and were not expressed in HCC and FTC. Further validation by quantitative PCR showed that ALDH1L1 genes, KLK1 and PVALB have greater sensitivity and specificity in distinguishing between benign from malignant thyroid; i.e., ALDH1L1, KLK1 and PVALB were present in the majority of HCA, while its expression was not detected in FTC and HCC. This project's initial goal is to validate, through immunohistochemistry, the expression of ALDH1L1 in HCA, FTA, HCC and FTC. In addition, the paper ALDH1L1 in the pathogenesis of thyroid tumors has not yet been characterized. Thus, later, we will clone the ALDH1L1 cDNA in the expression vector, followed by evaluate if the ectopic expression interferes with the processes associated with the tumors genesis and/or progression.

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