Publications by authors named "Thalita Alves"

4 Publications

  • Page 1 of 1

Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal.

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTp showed increased risk of structural disease (HR = 7.0, < 0.001) and DSM (HR = 10.1, = 0.001). Combined genotypes, BRAF/TERTp (HR = 6.8, = 0.003), BRAF/TERTp (HR = 3.2, = 0.056) and BRAF/TERTp (HR = 2.2, = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAF/TERTp (HR = 24.2, < 0.001) and BRAF/TERTp (HR = 11.5, = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTp regardless of BRAF status (BRAF/TERTp, log-rank < 0.001; BRAF/TERTp, log-rank < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAF/TERTp tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTp tumors were predisposed to recurrent structural disease and DSM.
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http://dx.doi.org/10.3390/cancers13092048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122921PMC
April 2021

Elevated TSH in a Thyroidectomized Patient: Differential Diagnosis Beyond Noncompliance with Treatment.

J Appl Lab Med 2019 03 20;3(5):903-908. Epub 2018 Jun 20.

Center of Thyroid Diseases and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo/UNIFESP, São Paulo, Brazil;

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http://dx.doi.org/10.1373/jalm.2018.026542DOI Listing
March 2019

Novel immunoassay for TSH measurement in rats.

Arch Endocrinol Metab 2017 Sept-Oct;61(5):460-463. Epub 2017 Sep 18.

Laboratório de Endocrinologia Molecular e Translacional, Divisão de Endocrinologia, Departamento de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brasil.

Measuring thyroid hormones is an important aspect for the study of metabolism and for monitoring diseases in both human and animal models. The traditional method for hormone measurement in rats is the radioimmunoassay (RIA). However, the RIA is associated with some practical disadvantages, including the use of radioactive material, the need for specialized equipment and expert staff, the short shelf-life of kits according to the half-life of the radioisotope and high costs. The objective of this study was to develop a new cost-effective method for measuring TSH levels in rats that avoids the use of radioactive material. We developed an in-house competitive immunoassay using a reference standard, polyclonal antibody produced in rabbits and biotinylated antigen. This method was tested in 64 Wistar rats that were divided into a control group (n = 41) and a group with hypothyroidism (n = 23). Our assay demonstrated an analytical sensitivity of 0.24 ng/mL (n = 12) and an intra-assay coefficient of variation (CV) of 8.9% for sera with TSH levels of 1.5 ng/mL and 13.2% for sera with TSH levels of 17.5 ng/mL (n = 14). The inter-assay CV was 13.5% for sera with TSH levels of 1.4 ng/mL and 14.5% for TSH levels of 18.2 ng/mL (n = 5). The analysis of mean TSH levels in control rats (5.06 ± 0.5701) and hypothyroid rats (51.09 ± 5.136) revealed a statistically significant difference (p < 0.001) between the groups. This method showed good sensitivity, can be automated and is low-cost compared with RIA. Our method offers a viable alternative for TSH measurement in rats.
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http://dx.doi.org/10.1590/2359-3997000000293DOI Listing
February 2018

Macrocalcitonin Is a Novel Pitfall in the Routine of Serum Calcitonin Immunoassay.

J Clin Endocrinol Metab 2016 Feb 8;101(2):653-8. Epub 2015 Dec 8.

Thyroid Disease Center and Laboratory of Molecular and Translational Endocrinology (T.G.A., T.S.K., J.H.Y., I.S.K., S.C.L., C.P.C., M.R.D.d.S., R.M.B.M., J.G.H.V., J.R.M.M.), Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04039-032 São Paulo, SP, Brazil; and Molecular Biology Division (T.G.A., M.C.Z.M., A.M., J.R.M.M.), Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04044-020 São Paulo, SP, Brazil.

Context: Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed even after complete surgical removal without evidence of a recurrent or persistent tumor.

Objective: To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease.

Patients And Methods: We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose.

Results: Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2-7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH.

Conclusions: For the first time, our results show the presence of a novel pitfall in the CT immunoassay: "macrocalcitonin." Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.
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http://dx.doi.org/10.1210/jc.2015-3137DOI Listing
February 2016
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