MARIA CLAUDIA NOGUEIRA ZERBINI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject A Lower Ki 67 Labelling Index (LI) Cut-Point Improves the Prognostic Assessment and Might Aid in the Diagnosis of Adult Adrenocortical Tumors(2018) MARTINS FILHO, Sebastiao N.; ALMEIDA, Madson Q.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio; FRAGOSO, Maria C.; ZERBINI, MariaconferenceObject LANGERHANS CELL HISTIOCYTOSIS: EVALUATION OF 36 BRAZILIAN CHILDREN AT A SINGLE INSTITUTION(2020) BOM, Ana; KUCZYNSKI, Ana Paula; MALUF FILHO, Paulo Taufi; ZERBINI, Maria Claudia Nogueira; OLANDOSKI, Marcia- Prenatal detection and postnatal management of an intranasal glioma(2012) OKUMURA, Maria; FRANCISCO, Rossana Pulcineli Vieira; LUCATO, Leandro Tavares; ZERBINI, Maria Claudia Nogueira; ZUGAIB, MarceloNasal gliomas are rare benign congenital midline tumors composed of heterotopic neuroglial tissue. They have potential for intracranial extension through a bony defect in the skull base. Neuroimaging is essential for identifying nasal lesions and for determining their exact location and any possible intracranial extension. Computed tomography is often the initial imaging study obtained because it provides good visualization of the bony landmarks of the skull base; it is not, however, well suited for soft tissue imaging. Magnetic resonance imaging has better soft tissue resolution and may be the best initial study in patients seen early in life because the anterior skull base consists of an unossified cartilage and may falsely appear as if there is a bony dehiscence on computed tomography. A frontal craniotomy approach is recommended if intracranial extension is identified, followed by a transnasal endoscopic approach for intranasal glioma. A case is presented of a huge fetal facial mass that was shown by ultrasound that protruded through the left nostril at 33 weeks of gestation. Computed tomography of the neonate suggested a transethmoidal encephalocele. Magnetic resonance imaging showed a huge mass occupying the nasopharynx and the nasal cavity and protruding externally to the face but ruled out bony discontinuity in the skull base and, therefore, any intracranial connection. The infant underwent an endoscopic resection of the mass via oral and nasal routes and pathologic examination revealed intranasal glioma.
- Analysis of clonal immunoglobulin chain gene rearrangement by the technique of polymerase chain reaction (PCR) to aid in the diagnosis of B-cell cutaneous lymphoproliferative processes(2023) GUIMARAES, Adriana Borba; SANCHES JUNIOR, Jose Antonio; ZERBINI, Maria Claudia; MIYASHIRO, Denis Ricardo; CURY-MARTINS, Jade; PEREIRA, Juliana; CULLER, Hebert Fabricio; CASTRO, Bruno
- KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism(2019) VILELA, Leticia A. P.; RASSI-CRUZ, Marcela; GUIMARAES, Augusto G.; MOISES, Caio C. S.; FREITAS, Thais C.; ALENCAR, Natalia P.; PETENUCI, Janaina; GOLDBAUM, Tatiana S.; MACIEL, Ana Alice W.; PEREIRA, Maria Adelaide A.; V, Giovanio Silva; PIO-ABREU, Andrea; ZERBINI, Maria Claudia N.; CAVALCANTE, Aline C. B. S.; CARNEVALE, Francisco C.; PILAN, Bruna; YAMAUCHI, Fernando; SROUGI, Vitor; TANNO, Fabio Y.; CHAMBO, Jose L.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; BORTOLOTTO, Luiz A.; DRAGER, Luciano F.; ALMEIDA, Madson Q.Context: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. Objective: To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA. Methods: We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. Results: KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.GIu145GIn (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P= 0.0001), and 64.9% had HT duration <10 years (P= 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004). Conclusion: The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.
conferenceObject Morphological, Immunohistochemical and Cytogenetic Bone Marrow Characterization of 12 Patients with Acquired Aplastic Anemia (AAA) That Progressed to Myelodysplastic Syndromes (MDS)(2017) MARCHESI, Raquel; VELLOSO, Elvira; GARANITO, Marlene; SIQUEIRA, Sheila; NETO, Raymundo Azevedo; KUMEDA, Cristina; ZERBINI, Maria Claudia- Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas(2021) PETENUCI, Janaina; GUIMARAES, Augusto G.; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; AFONSO, Ana Caroline F.; PEREIRA, Maria Adelaide A.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SOARES, Silvia C.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose L.; I, Roberto Lopes; DENES, Francisco T.; HOFF, Ana O.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and Methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.
- Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus(2020) BERTONHA, Fernanda Bernardi; BANDO, Silvia Yumi; FERREIRA, Leandro Rodrigues; CHACCUR, Paulo; VINHAS, Christiana; ZERBINI, Maria Claudia Nogueira; CARNEIRO-SAMPAIO, Magda Maria; MOREIRA-FILHO, Carlos AlbertoThe human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1st and 2nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through Weighted Gene Co-expression Network Analysis (WGCNA) and TF-miRNA-mRNA integrative analysis we studied the transcriptome of neonate and infant thymic tissues grouped by age: 0-30 days (A); 31 days-6 months (B); 7-12 months (C); 13-18 months (D); 19-31 months (E). Age-related transcriptional modules, hubs and high gene significance (HGS) genes were identified, as well as TF-miRNA-hub/HGS co-expression correlations. Three transcriptional modules were correlated with A and/or E groups. Hubs were mostly related to cellular/metabolic processes; few were differentially expressed (DE) or related to T-cell development. Inversely, HGS genes in groups A and E were mostly DE. In A (neonate) one third of the hyper-expressed HGS genes were related to T-cell development, against one-twentieth in E, what may correlate with the early neonatal depletion and recovery of thymic T-cell populations. This genomic mechanism is tightly regulated by TF-miRNA-hub/HGS interactions that differentially govern cellular and molecular processes involved in the functioning of the neonate thymus and in the beginning of thymic decline.
- Targeting the polarization of tumor-associated macrophages and modulating mir-155 expression might be a new approach to treat diffuse large B-cell lymphoma of the elderly(2019) POLES, Wagner A.; NISHI, Erika E.; OLIVEIRA, Mariana B. de; EUGENIO, Angela I. P.; ANDRADE, Tathiana A. de; CAMPOS, Antonio Hugo F. M.; CAMPOS JR., Ruy R. de; VASSALLO, Jose; ALVES, Antonio C.; NETO, Cristovam Scapulatempo; PAES, Roberto Antonio Pinto; LANDMAN, Gilles; ZERBINI, Maria Claudia N.; COLLEONI, Gisele W. B.Aging immune deterioration and Epstein-Barr (EBV) intrinsic mechanisms play an essential role in EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV+DLBCLe) pathogenesis, through the expression of viral proteins, interaction with host molecules and epigenetic regulation, such as miR-155, required for induction of M1 phenotype of macrophages. This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV+DLBCLe and EBV-negative DLBCL patients. We studied 28 EBV+DLBCLe and 65 EBV-negative DLBCL patients. Tumor-associated macrophages (TAM) were evaluated by expression of CD68, CD163 and CD163/CD68 ratio (degree of M2 polarization), using tissue microarray. RNA was extracted from paraffin-embedded tumor samples for miR-155 relative expression study. We found a significantly higher CD163/CD68 ratio in EBV+DLBCLe compared to EBV-negative DLBCL. In EBV-negative DLBCL, CD163/CD68 ratio was higher among advanced-staged/high-tumor burden disease and overexpression of miR-155 was associated with decreased polarization to the M2 phenotype of macrophages. The opposite was observed in EBV+DLBCLe patients: we found a positive association between miR-155 relative expression and CD163/CD68 ratio, which was not significant after outlier exclusion. We believe that the higher CD163/CD68 ratio in this group is probably due to the presence of the EBV since it directly affects macrophage polarization towards M2 phenotype through cytokine secretion in the tumor microenvironment. Therapeutic strategies modulating miR-155 expression or preventing immuno-regulatory and pro-tumor macrophage polarization could be adjuvants in EBV+DLBCLe therapy since this entity has a rich infiltration of M2 macrophages in its tumor microenvironment.
conferenceObject Confocal Microscopy Image Analysis of Pancreatic beta-Cells K-ATP Channel Proteins in Congenital Hyperinsulinism (CHI)(2012) LOVISOLO, S. M.; GARIPPO, A. L.; GUEDES, F.; ZERBINI, M. C.Background: CHI is a life-threatening disorder of glucose metabolism of neonates characterized by serum insulin levels unresponsive to blood glucose concentrations. Pancreatic ß-cells regulates insulin secretion through ATP sensitive potassium channels (KATP channel) formed by sulfonylurea receptor 1 (SUR1) and potassium inward rectifying 6.2 (Kir 6.2) proteins. The ß-cell K ATP channel dependent CHI is classically associated with loss-of-function mutations of these subunits genes. In a previous study [1], no mutations in the Kir6.2 gene and in the 33-37 exons hot spot region of the SUR1 gene were identified in these patients. The aim of this study is to investigate if these subunits were present in the ß-cells of CHI patients. Design: Pancreatic surgical paraffin tissue from 7 neonates (3F/4M, 4-13 mo) with CHI and 8 autopsy pancreatic control tissue (5F/3M, 4-11 mo) were included in the study. Confocal microscopy double-staining immunofluorescence (insulin/SUR1 and insulin/Kir6.2) was performed in order to detect each protein specifically in the ß-cells All sections were analyzed under a Zeiss 510 Meta confocal laser scanning microscope (63x). At least 10 different endocrine islets were captured to evaluate the expression of either Kir6.2 or SUR1 (green-488nm) and insulin (red-633nm). Co-expression of insulin/SUR1 and insulin/Kir6.2 was analysed visually (green x red→yellow) and through correlation Pearson’s coefficient(PC) that estimates the goodness of rate association of the two fluorochromes. PC was compared among cases and controls using a nonparametric method (Mann-Whitney). Results: Visual observation clearly revealed the presence of Kir6.2 and SUR1 in a granular cytoplasmic pattern in the ß-cells of cases and controls. Nevertheless, overlap of insulin/Kir6.2 and insulin/SUR1 seemed to be more constant and uniform in controls than in CHI cases, confirmed by the analysis through PC showing a statistically significant decrease in Kir6.2 (P= 0.0084) and SUR1 (P= 0.041) in the ß-cells of CHI patients. Conclusions: This is the first demonstration of K ATP channels subunits Kir6.2 and SUR1 in the pancreatic ß-cells of CHI patients using an in situ method. Our results show that both subunits were present in the ß-cells, but are under-expressed in CHI patients compared to controls, adding a new information to this rare condition with a complex pathogenesis.