ERIKA URBANO DE LIMA
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- Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression(2013) GALRAO, A. L.; SODRE, A. K.; CAMARGO, R. Y.; FRIGUGLIETTI, C. U.; KULCSAR, M. A.; LIMA, E. U.; MEDEIROS-NETO, G.; RUBIO, I. G. S.DNA methylation regulates gene expression. Aberrant methylation plays an important role in human tumorigenesis. We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non-tumor tissues. Thus, in this study we investigated whether the methylation of the CpG-island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors. Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors (T) along with matched non-tumor (NT) areas were determined by semiquantitative methylation specific-PCR. NIS methylation was detected in all samples. Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status. Highest methylation levels and frequencies were detected in the 5' region of the CpG-island decreasing toward the 3' end. Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression. No quantitative correlation was detected between methylation levels and mRNA expression in any the groups. The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non-homogeneous methylation pattern along the CpG island. Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted.
- BRAF: A Tool in the Decision to Perform Elective Neck Dissection?(2013) DUTENHEFNER, Simone E.; MARUI, Suemi; SANTOS, Andre B. O.; LIMA, Erika Urbano de; INOUE, Milton; BRANDAO NETO, Jose S.; SHIANG, Christina; FUKUSHIMA, Julia T.; CERNEA, Claudio R.; FRIGUGLIETTI, Celso U. M.Background: Some studies have demonstrated a correlation between the presence of a BRAF mutation and aggressive characteristics, including lymph node metastasis in papillary thyroid carcinoma (PTC). Prophylactic central neck dissection (CND) has been proposed for treatment of PTC. Given the potential complications of CND, we undertook a prospective study to determine the correlation between the BRAF mutation and lymph node metastasis. Methods: A total of 51 patients with PTC underwent total thyroidectomy and routine prophylactic CND. All patients were tested for the BRAF mutation. Results: Positive lymph nodes were found in 54.9% of patients. The BRAF mutation was found in 15 patients (29%). BRAF was not correlated with lymph node metastases. Lymph node metastases were correlated with multifocality (p=0.005) and angiolymphatic invasion (p=0.003) in univariate analysis. Age was also significant in multivariate analysis. Conclusions: Testing for the BRAF mutation does not help in deciding whether or not to perform CND.
- Papillary carcinoma in thyroglossal duct cyst: role of fine needle aspiration and frozen section biopsy to guide surgical approach(2014) DANILOVIC, Debora L. S.; MARUI, Suemi; LIMA, Erika U.; LUIZ, Arthur V. C.; BRESCIA, Marilia D. E. G.; MOYSES, Raquel A.; CERNEA, Claudio R.; BRANDAO, Lenine G.; CHAMMAS, Maria C.; SANTOS, Andre B. O.
- Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection(2012) DANILOVIC, Debora L. S.; MENDES-CORREA, Maria C.; LIMA, Erika U.; ZAMBRINI, Heverton; BARROS, Raffaelle K.; MARUI, SuemiBackground: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. Aims: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. Methods: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. - 318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Results: Eight AT repetitions in 3' UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). Conclusion: CTLA-4 gene polymorphisms were associated to HCVinfection. Eight AT repetitions were more prevalent in HCV-infected subjects. - 318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3' UTR region favoured severe necroinflammatory activity scores in liver biopsies.
- Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma(2014) DANILOVIC, Debora L. S.; LIMA, Erika U.; DOMINGUES, Regina B.; BRANDAO, Lenine G.; HOFF, Ana O.; MARUI, SuemiObjective: The p. V600E BRAF and RAS mutations are found in 30-80% of differentiated thyroid carcinoma (DTC). BRAF mutation has been associated with poor prognosis. This study investigated the role of molecular studies in preoperative diagnosis of DTC and the association of p. V600E mutation with prognostic factors. Design: Prospective study. Methods: A total of 202 patients with cytological diagnosis of Bethesda III-VI underwent preoperative molecular studies and subsequent thyroidectomy. p. V600E and RAS mutations were studied in the cytology smears, using real-time PCR genotyping technique. The BRAF mutation (BRAF(+) or BRAF(-)) was correlated with histological and clinical findings. Results: Molecular study of 172 nodules with Bethesda III-V cytology improved negative predictive value and accuracy of Bethesda III and IV diagnosis. BRAF mutation was present in 65% of 94 DTC and p. Q61R NRAS in one. Except for age, BRAF C and BRAF(1) did not differ in sex, tumor size, histological subtype, multifocality, vascular invasion, extrathyroidal extension, or prognostic staging. Among papillary carcinomas, lymph node (LN) metastasis was diagnosed in 23% BRAF C and 37% BRAF K. Distant metastasis occurred in four BRAF(-) . Recurrent or persistent disease was more frequent in BRAF K (26.7 vs 3.3% BRAF(+), P=0.002) along follow-up of 29.8 +/- 10 months. BRAF(+) patients without LN metastasis by pre-operative evaluation submitted to thyroidectomy with central neck dissection ( CND) had more frequent LN metastasis ( 45 vs 5% no CND, P=0.002), but no difference in clinical outcome was observed. Conclusions: Pre-operative identification of BRAF mutation improved cytological diagnosis of DTC, but it was not associated with poor prognostic factors. Prophylactic CND did not guarantee better outcome in BRAF C patients.
- New mutation in the PTEN gene in a Brazilian patient with Cowden's syndrome(2012) LIMA, Erika U. de; SOARES, Ibere C.; DANILOVIC, Debora L. S.; MARUI, SuemiCowden syndrome is characterized by hamartomatous polyps, trichilemmomas, increased risk of developing neoplasms, and is associated with germline mutations in the PTEN gene. We searched for germline mutations in PTEN in a 49-year-old female patient who presented trichilemmoma with previous history of breast carcinoma, and thyroidectomy for a thyroid nodule. We also searched for somatic mutations in breast and thyroid tumoral tissues. DNA was extracted from peripheral leukocytes, paraffin samples of breast carcinoma, and cytological smears of thyroid nodule fine-needle aspiration biopsy, whose final histopathological diagnosis was adenomatous goiter. PTEN was amplified and sequenced. We identified a novel mutation, due to a T>A inversion at position 159 and A>T inversion at position 160, leading to valine-to-aspartic acid substitution at position 53. The p.Val53Asp was also found in homozygous state in samples obtained from adenocarcinoma breast and thyroid biopsy, denoting loss of heterozygosity. Here, we demonstrated a novel germline mutation in PTEN, as well as somatic loss of the wild-type PTEN allele in breast and thyroid tumors in a patient with Cowden syndrome.