ERICKA BARBOSA TRARBACH
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Genotype analysis of the human endostatin variant p.D104N in benign and malignant adrenocortical tumors(2012) MARIANI, Beatriz Marinho de Paula; TRARBACH, Ericka Barbosa; RIBEIRO, Tamaya Castro; PEREIRA, Maria Adelaide Albergaria; MENDONCA, Berenice Bilharinho; FRAGOSO, Maria Candida Barisson VillaresOBJECTIVE: Endostatin is a potent endogenous inhibitor of angiogenesis. It is derived from the proteolytic cleavage of collagen XVIII, which is encoded by the COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism p.D104N impairs the activity of endostatin, resulting in a decreased ability to inhibit angiogenesis. This polymorphism has been previously analyzed in many types of cancer and has been considered a phenotype modulator in some benign and malignant tumors. However, these data are controversial, and different results have been reported for the same tumor types, such as prostate and breast cancer. The purpose of this study was to genotype the p.D104N variant in a cohort of pediatric and adult patients with adrenocortical tumors and to determine its possible association with the biological behavior of adrenocortical tumors. METHODS: DNA samples were obtained from 38 pediatric and 56 adult patients (0.6-75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or fresh frozen tissue samples were unavailable. Restriction fragment length polymorphism analysis was used to genotype the patients and 150 controls. The potential associations of the p.D104N polymorphism with clinical and histopathological features and oncologic outcome (age of onset, tumor size, malignant tumor behavior, and clinical syndrome) were analyzed. RESULTS: Both the patient group and the control group were in Hardy-Weinberg equilibrium. The frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD), 15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3% and 2.0%, respectively. We did not observe any association of this variant with clinical or histopathological features or oncologic outcome in our cohort of pediatric and adult patients with adrenocortical tumors.
bookPart Biologia molecular dos tumores endócrinos(2013) LERARIO, Antonio Marcondes; FRAGOSO, Maria Candida Barisson; BRITO, Luciana Pinto; MARTIN, Regina Matsunaga; TRARBACH, Erika Barbosa; MARUI, Suemi; TOLEDO, Rodrigo de Almeida; DOMENICE, Sorahia; MENDONçA, Berenice Bilharinho de- Transcriptome analysis showed a Differential signature between invasive and non-invasive corticotrophinomas(2017) ARAUJO, Leonardo Jose Tadeu de; LERARIO, Antonio Marcondes; CASTRO, Margaret de; MARTINS, Clarissa Silva; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; FRAGOSO, Maria Candida Barisson VillaresACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushing's disease (CD)] is the most common cause of endogenous Cushing's syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (approximate to 80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, >= 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF-beta and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
- Filamin A and DRD2 expression in corticotrophinomas(2019) SICKLER, Thais; TRARBACH, Ericka Barbosa; FRASSETTO, Fernando Pereira; DETTONI, Juliano Bertollo; ALVES, Venancio Avancini Ferreira; FRAGOSO, Maria Candida Barisson Villares; MACHADO, Marcio Carlos; CARDOSO, Ellison Fernando; BRONSTEIN, Marcello Delano; GLEZER, AndreaPurposeFilamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics.MethodsDRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0-300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery.ResultsTwenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion.ConclusionsIn our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.
- Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis(2019) WANICHI, Ingrid Quevedo; MARIANI, Beatriz Marinho de Paula; FRASSETTO, Fernando Pereira; SIQUEIRA, Sheila Aparecida Coelho; MUSOLINO, Nina Rosa de Castro; CUNHA-NETO, Malebranche Berardo Carneiro; OCHMAN, Gilberto; CESCATO, Valter Angelo Sperling; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; BRONSTEIN, Marcello Delano; FRAGOSO, Maria Candida Barisson VillaresPurposeCushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.MethodsDNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n=630).ResultsWe identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p <= 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p<0.1x10(-4)). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p<0.1x10(-4)).ConclusionOur data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.
- New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations(2019) FAGUNDES, Gustavo F. C.; PETENUCI, Janaina; JR, Delmar M. Lourenco; TRARBACH, Ericka B.; PEREIRA, Maria Adelaide A.; D'EUR, Joya Emilie Correa; HOFF, Ana O.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Context: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-yearold boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.
- Transcriptome Analysis Showed a Differential Signature Between Invasive and Non-invasive Corticotrophinomas (vol 8, 55, 2017)(2019) ARAUJO, Leonardo Jose Tadeu de; LERARIO, Antonio Marcondes; CASTRO, Margaret de; MARTINS, Clarissa Silva; BRONSTEIN, Marcello Delano; MACHADO, Marcio Carlos; TRARBACH, Ericka Barbosa; FRAGOSO, Maria Candida Barisson Villares