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
10 resultados
Resultados de Busca
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- 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
- A model for preservation of thymocyte-depleted thymus(2023) DIAS, A. S.; DAMACENO-RODRIGUES, N. R.; GIMENEZ, T. M.; OLIVEIRA, P. M.; ZERBINI, M. C.; CARNEIRO-SAMPAIO, M.; FILHO, V. Odone; JATENE, M. B.; VASCONCELOS, D. M.; ROCHA, V.; NOVAK, E. M.DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196 & DEG;C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3 x 106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
- B cell subsets in thymus from infants with Down syndrome(2023) SILVEIRA-LESSA, Ana Lucia; PALMEIRA, Patricia; VINHAS, Christiana; FERREIRA, Leandro; CHACCUR, Paulo; ZERBINI, Maria Claudia N.; CARNEIRO-SAMPAIO, Magda
- Core Needle Biopsy in Lymphoma Diagnosis The Diagnostic Performance and the Role of the Multidisciplinary Approach in the Optimization of Results(2023) GONCALVES, Marianne de C.; OLIVEIRA, Claudia Regina G. C. M. de; SANDES, Alex E.; RODRIGUES, Celso A.; NOVIS, Yana; VIANA, Publio C. C.; SERRA, Marcia M. P.; ZERBINI, Maria Claudia N.To compare the diagnostic accuracy of core needle biopsies (CNBs) and surgical excisional biopsies (SEBs), samples of lymphoid proliferation from a single institution from 2013 to 2017 (N=476) were divided into groups of CNB (N=218) and SEB (N=258). The diagnostic accuracy of these samples was evaluated as a percentage of conclusive diagnosis, according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. The contribution of clinical data, the assessment of sample adequacy by a pathologist during the procedure, the number and size of fragments, the needle gauge, the ancillary tests, and the type of lymphoid proliferation were also examined. The diagnostic accuracy of SEB was 97.3% and CNB 91.3% (P=0.010). Additional factors considered essential for establishing the final diagnosis in some cases were: clinical information (20.6% CNB, 7.4% SEB; P<0.001); immunohistochemistry (96.3% CNB, 91.5% SEB; P=0.024); flow cytometry (12% CNB, 6.8% SEB; P=0.165); and other complementary tests (8.2% CNB, 17.3% SEB; P=0.058). Factors that did not influence performance were the evaluation of sample adequacy during the procedure, the number and size of fragments, and the needle gauge. Increased percentage of nondiagnostic CNB was observed in T-cell lymphomas (30%), followed by classic Hodgkin lymphoma (10.6%). The main limitation of CNB was the evaluation of morphologically heterogenous diseases. CNB is useful and safe in lymphoma diagnosis provided it is carried out by a team of experienced professionals. Having an interventional radiology team engaged with pathology is an essential component to achieve adequate rates of specific diagnoses in CNB specimens.
- Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening(2023) MACIEL, Ana Alice W.; FREITAS, Thais C.; FAGUNDES, Gustavo F. C.; PETENUCI, Janaina; VILELA, Leticia A. P.; BRITO, Luciana P.; GOLDBAUM, Tatiana S.; ZERBINI, Maria Claudia N.; LEDESMA, Felipe L.; TANNO, Fabio Y.; SROUGI, Victor; CHAMBO, Jose L.; PEREIRA, Maria Adelaide A.; COELHO, Fernando M. A.; CAVALCANTE, Aline C. B. S.; CARNEVALE, Francisco C.; PILAN, Bruna; PIO-ABREU, Andrea; V, Joao Silveira; CONSOLIM-COLOMBO, Fernanda M.; BORTOLOTTO, Luiz A.; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso; DRAGER, Luciano F.; MENDONCA, Berenice B.; ALMEIDA, Madson Q.Context Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/mu IU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.
- Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening (Nov, dgac679, 2022)(2023) MACHEI, A. A. W.; FREITAS, T. C.; FAGUNDES, G. F. C.; PETENUCI, J.; VILELA, L. A. P.; BRITO, L. P.; GOLDBAUM, T. S.; ZERBINI, M. C. N.; LEDESMA, F. L.; YANNO, F. Y.; SROUGI, V; CHAMBO, J. L.; PEREIRA, M. A. A.; COELHO, F. M. A.; CAVALCANTE, A. C. B. S.; CARNEVALE, F. C.; PILAN, B.; PIO-ABREU, A.; V, J. Silveira; CONSOLIM-COLOMBO, F. M.; BORTOLOTTO, L. A.; LATRONICO, A. C.; V, M. C. B. Fragoso; DRAGER, L. F.; MENDONCA, B. B.; ALMEIDA, M. Q.
- Morphological Harbingers of ARMC5-Pathogenic Variant-Related Bilateral Macronodular Adrenocortical Disease(2023) BOTELHO, Maria Luiza Anhaia de Arruda; NISHI, Mirian Yumie; RIBEIRO, Karina Braga; ZERBINI, Maria Claudia NogueiraBilateral macronodular adrenocortical disease (BMAD) is a neoplastic disease associated with a high frequency of germline disease. Armadillo repeat containing 5 (ARMC5) pathogenic variants (PVs) have not been widely studied to determine the morphological and immunohistochemical characteristics of BMAD. We carried out a detailed morphologic review of 22 surgical specimens excised from patients with BMAD and compared them with PV of ARMC5 (PV + , n = 14) and those without (PV - , n = 8), and further comparing them with a control group of adrenals excised from patients with renal cancer (n = 11). No patients presented with a genetic syndrome related to BMAD. Overt Cushing's syndrome was present in 12/22 patients, 10 PV + and 2 PV - (p = 0.074). We also evaluated the expression of Ki-67, BCL-2, BAX, p53, CYP11B1, and ARMC5 protein. The pseudo-glandular and trabecular architectural patterns were strongly associated with the PV + group (both p < 0.001), as well as capsular extrusion (p < 0.001). There was no predictive value in the distinction of ARMC5 variants in Hsiao subtyping. ARMC5 diffuse cytoplasmic staining was observed in all 11 control samples. The ARMC5 expression was significantly lower in BMAD than in the control group (p < 0.001). In all the specimens, expression of BCL-2 was identified only in the medulla, and expression of BAX was observed in adrenocortical cells. CYP11B1 diffuse immunoexpression was identified in all the specimens of BMAD and in the fasciculata zone in the control group. The mitotic count and Ki-67 proliferation index was very low in all three groups (controls, PV + , and PV - BMAD). None of the specimens stained positive for the p53 protein. Although our series is limited, the presence of pseudo-glandular and/or trabecular patterns and capsular extrusion indicated the presence of pathogenic variants of ARMC5 in BMAD. The gland enlargement does not seem to be related to the increase of mitotic count or a higher proliferation index (Ki-67).
- Comparison of two immunohistochemical staining protocols for ALK demonstrates non-inferiority of a 5A4 clone-based protocol versus an ALK01 clone-based protocol for the diagnosis of ALK plus anaplastic large cell lymphoma(2023) FERNANDEZ-POL, Sebastian; FERREIRA, Cristiane R.; MANOHAR, Vidhya; SANCHES, Jose Antonio; LAGE, Luis A. P. C.; PEREIRA, Juliana; ZERBINI, Maria C. N.; GRATZINGER, Dita; NATKUNAM, YasodhaDetection of ALK rearrangement and/or expression of the ALK protein is an essential component in the evaluation of many neoplasms. Variability has been reported in the ability of different antibody clones to detect ALK expression. The ALK01 clone is commonly used to detect ALK expression in ALK-positive anaplastic large cell lymphoma (ALK + ALCL). However, this clone has been shown to lack sensitivity when used for solid tumors. The aim of this study was to determine if our high-sensitivity 5A4-based immunohistochemistry protocol is non-inferior to our ALK01-based protocol for the detection of ALK expression in ALK + ALCL. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 primary cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK + ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.
- & beta;-Catenin-Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer(2023) MOHAN, Dipika R.; BORGES, Kleiton S.; FINCO, Isabella; LAPENSEE, Christopher R.; REGE, Juilee; SOLON, April L.; III, Donald W. Little; ELSE, Tobias; ALMEIDA, Madson Q.; DANG, Derek; HAGGERTY-SKEANS, James; APFELBAUM, April A.; VINCO, Michelle; WAKAMATSU, Alda; MARIANI, Beatriz M. P.; AMORIM, Larissa Costa; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; ZERBINI, Maria Claudia N.; LAWLOR, Elizabeth R.; OHI, Ryoma; AUCHUS, Richard J.; RAINEY, William E.; MARIE, Suely K. N.; GIORDANO, Thomas J.; VENNETI, Sriram; FRAGOSO, Maria Candida Barisson Villares; BREAULT, David T.; LERARIO, Antonio Marcondes; HAMMER, Gary D.Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal out-comes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent 3-catenin-activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific 3-catenin-containing com-plexes, and the epigenome. On chromatin, 3-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, 3-catenin bound histone methyltransfer-ase EZH2. SF1/3-catenin and EZH2/3-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/ 3-catenin from chromatin and favored EZH2/3-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities. Significance: Oncogenic 3-catenin can use tissue-specific part-ners to regulate cellular differentiation programs that can be reversed by epigenetic therapies, identifying epigenetic control of differentiation as a viable target for 3-catenin-driven cancers.
conferenceObject Retrospective Analysis of Prognostic Factors in Pediatric Patients with Adrenocortical Tumor from Unique Tertiary Center with Long-Term Follow-up(2023) BACHEGA, Fernanda; SUARTZ, Caio; ALMEIDA, Madson; BRONDANI, Vania; CHARCHAR, Helaine; LACOMBE, Amanda; MARTINS-FILHO, Sebastiao; SOARES, Ibere; ZERBINI, Maria Claudia; DENES, Francisco; MENDONCA, Berenice; LOPES, Roberto; LATRONICO, Ana Claudia; FRAGOSO, Maria Candida