Luciana Pinto Brito

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, San Paulo, São Paulo, Brazil

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Publications (9)22.86 Total impact

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    ABSTRACT: Background Anti-Mullerian hormone is marker of ovarian and testicular reserve. The clinical use of this hormone requires proper standardization of reference intervals. The aims of this study were to validate the Anti-Mullerian hormone Gen II immunoassay, to establish Anti-Mullerian hormone reference intervals in healthy subjects, and to evaluate the influence of hormonal contraceptives, smoking, and body mass index on Anti-Mullerian hormone. Methods The validation of the Anti-Mullerian hormone Gen II assay (Beckman Coulter Company, TX, USA) was performed using a simplified protocol recommended by Clinical Laboratory Standard Institute. One-hundred and thirty-three healthy females and 120 males were prospectively selected for this study. Results The analytical and functional sensitivities of the Anti-Mullerian hormone Gen II immunoassay were 0.02 and 0.2ng/mL, respectively. Intra-assay coefficients ranged from 5.2 to 9.0%, whereas inter-assay precision ranged from 4.6 to 7.8% at different concentrations. In females, Anti-Mullerian hormone showed progressive decline with increasing age (r=-0.4, p<0.001), whereas in males, age showed no influence on Anti-Mullerian hormone concentrations. In females, Anti-Mullerian hormone concentrations did not differ between users and non-users of hormonal contraceptives, smokers, and non-smokers and obese and lean individuals. However, there was a negative and significant correlation between Anti-Mullerian hormone and body mass index in males (r=-0.3, p=0.008). Conclusions Anti-Mullerian hormone Gen II assay was reliable for determining serum Anti-Mullerian hormone concentrations. Anti-Mullerian hormone concentrations declined with aging and presented a wide inter-individual variability. The lack of influence of hormonal contraceptives, smoking, and obesity on Anti-Mullerian hormone in both sexes allowed us to refine the normative concentrations for the Brazilian population.
    Annals of Clinical Biochemistry 09/2014; 52(1). DOI:10.1177/0004563214554462 · 2.08 Impact Factor
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    ABSTRACT: Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far.
    BMC Endocrine Disorders 05/2014; 14(1):42. DOI:10.1186/1472-6823-14-42 · 1.67 Impact Factor
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    ABSTRACT: FGFR4 overexpression has been demonstrated in human neoplasms, including adrenocortical tumors (ACTs). However, the molecular mechanisms underlying FGFR4 upregulation and their influence in the outcome have not been fully addressed in ACTs. To evaluate FGFR4 expression in a Brazilian cohort of ACT patients and to verify if FGFR4 gene amplification is associated with overexpression. 57 tumors from 25 children and 32 adults (37 adenomas and 20 carcinomas) were studied. Gene expression was evaluated by qRT-PCR. Gene amplification was assessed by MLPA. In pediatric ACTs, FGFR4 transcripts were overexpressed in all except 3 cases (88%). In contrast, in adults, FGFR4 overexpression was detected in 47% of samples (15 out of 32) and was significantly higher in carcinomas [9.35 (0.21 - 35.73) vs. 1.44 (0.53 - 9.85), for carcinomas and adenomas, respectively; p=0.004)]. An increased FGFR4 copy number was identified in 8.3% (1 of 12) and 54.5% (6 of 11) of adult adenomas and carcinomas, respectively (p=0.027). In adults, FGFR4 overexpression and amplification were predictors of malignancy (p=0.049 and p=0.008, respectively). FGFR4 overexpression was demonstrated in both pediatric and adult ACTs suggesting an important role in adrenocortical tumorigenesis. In adults, FGFR4 overexpression was detected mainly in carcinomas and was associated with locus amplification in most cases.
    Endocrine Related Cancer 01/2012; 19(3):L11-3. DOI:10.1530/ERC-11-0231 · 4.91 Impact Factor
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    ABSTRACT: A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients - 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.
    European Journal of Endocrinology 11/2011; 166(1):61-7. DOI:10.1530/EJE-11-0806 · 3.69 Impact Factor
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    ABSTRACT: The occurrence of metachronous adrenocortical carcinoma has rarely been described. We report a case of a child with virilizing adrenocortical metachronous tumors that, despite several metastases, presented long-term survival (15 years). We analyzed in this tumor IGF2, IGF1R and FGFR4 gene expression, and evaluated the presence of p.R337H germline p53 mutation and somatic CTNNB1 mutation. IGF2 gene was over-expressed in both left (Weiss score 5) and right (Weiss 7) adrenocortical tumors. IGF1R expression levels were higher in the right adrenocortical tumor. FGFR4 over-expression was also detected in the right adrenocortical tumor. In addition, this patient harbors the germline p.R337H p53 mutation and loss of heterozygosity (LOH) was detected in the tumors. No somatic CTNNB1 mutations were found in both tumors. In conclusion, we demonstrated in this unusual case the over-expression of growth signaling pathways, which are molecular mechanisms previously related to adrenocortical tumorigenesis. Furthermore, the absence of somatic CTNNB1 mutations, which is a molecular marker of poor prognosis in adults, might be related to the long-term survival of this patient.
    Arquivos brasileiros de endocrinologia e metabologia 02/2011; 55(1):72-7. DOI:10.1590/S0004-27302011000100010 · 0.68 Impact Factor
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    ABSTRACT: Activating mutations in exon 3 of the β-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between β-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the β-catenin gene was screened for mutations, and the expression of the β-catenin gene and PROP1 was evaluated. β-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and β-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and β-catenin immunohistochemistry was performed on 11 samples. Mutations in the β-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71% of the tumors with β-catenin mutations and in 40% of the tumors without mutations, and β-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. We found evidence of β-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear β-catenin staining pattern regardless of the presence of a β-catenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort.
    Clinics (São Paulo, Brazil) 01/2011; 66(11):1849-54. DOI:10.1590/S1807-59322011001100001 · 1.42 Impact Factor
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    ABSTRACT: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing's disease after transsphenoidal surgery. The objective was to investigate whether there is an association between the postoperative outcome of Cushing's disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing's disease. Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 μg/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing's disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing's disease, respectively.
    The Journal of Clinical Endocrinology and Metabolism 10/2010; 95(10):E271-9. DOI:10.1210/jc.2010-0047 · 6.31 Impact Factor
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    Clinics (São Paulo, Brazil) 09/2010; 65(10):1059-60. DOI:10.1590/S1807-59322010001000024 · 1.42 Impact Factor
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    ABSTRACT: Primary pigmented nodular adrenocortical disease (PPNAD) is the main endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH) in adrenocortical tumorigenesis remains controversial. The aim of the present study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a patient with Carney complex. The LOH was investigated using a PRKAR1A informative intragenic marker by GeneScan software analysis in DNA obtained from laser-captured microdissected cells of several adrenal nodules. Patients: A young adult male patient with Carney complex and his family were studied. A novel heterozygous mutation (p. Y21X) was identified at PRKAR1A in blood DNA of the male proband and his relatives. No PRKAR1A LOH was evidenced in the laser-captured microdissected cells from PPNAD tissue by different methodologies. We identified a new PRKAR1A nonsense mutation and in addition we did not evidence PRKAR1A LOH in laser-captured nodules cells, suggesting that adrenocortical tumorigenesis in PPNAD may occurs apart from the second hit.
    Arquivos brasileiros de endocrinologia e metabologia 12/2008; 52(8):1257-63. DOI:10.1590/S0004-27302008000800009 · 0.68 Impact Factor