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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- Image-guided lymph node core needle biopsy in mycosis fungoides/Sezary syndrome: Direct comparison to surgical excision(2022) CURY-MARTINS, Jade; COUTO NETTO, Sergio Dias do; CASTRO, Stephanie Catarine Carqueijo de; SIQUEIRA, Sheila Aparecida Coelho; GIANNOTTI, Marcelo Abrantes; ZERBINI, Maria Claudia Nogueira; PEREIRA, Juliana; CULLER, Hebert; TEIXEIRA JR., Frederico Jose Ribeiro; MENEZES, Marcos Roberto de; SANCHES, Jose Antonio
- Retrospective Analysis of Prognostic Factors in Pediatric Patients with Adrenocortical Tumor from Unique Tertiary Center with Long-Term Follow-Up(2022) BACHEGA, Fernanda S.; V, Caio Suartz; ALMEIDA, Madson Q.; BRONDANI, Vania B.; CHARCHAR, Helaine L. S.; LACOMBE, Amanda M. F.; MARTINS-FILHO, Sebastiao N.; SOARES, Ibere C.; ZERBINI, Maria Claudia N.; DENES, Francisco T.; MENDONCA, Berenice; I, Roberto Lopes; LATRONICO, Ana Claudia; V, Maria Candida B. FragosoPediatric adrenocortical tumors (PACTs) represent rare causes of malignancies. However, the south/southeast regions of Brazil are known to have a high incidence of PACTs because of the founder effect associated with a germline pathogenic variant of tumor suppressor gene TP53. We aimed to retrospectively analyze the types of variables among hormone production, radiological imaging, tumor staging, histological and genetic features that were associated with the occurrence of malignancy in 95 patients (71% females) with PACTs from a unique center. The worst prognosis was associated with those aged > 3 years (p < 0.05), high serum levels of 11-desoxicortisol (p < 0.001), tumor weight >= 200 g (p < 0.001), tumor size >= 5 cm (p < 0.05), Weiss score >= 5 (p < 0.05), Wieneke index >= 3 (p < 0.001) and Ki67 >= 15% (p < 0.05). Furthermore, patients with MacFarlane stage IV had an overall survival rate almost two times shorter than patients with other stages (p < 0.001). Additionally, the subtractions of BUB1B-PINK1 (<6.95) expression (p < 0.05) and IGF-IR overexpression (p = 0.0001) were associated with malignant behavior. These results helped identify patients who are likely to have an aggressive course; further multicenter prospective studies are required to confirm our results. In conclusion, PACTs with these patterns of prognostic factors could be treated using an adjuvant approach that may improve the overall survival in such patients.
- High Tumor Mutation Burden in Epigenetic Regulatory Genes Predicts Decreased Overall Survival in Nodal Peripheral T-Cell Lymphomas(2022) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTI, Jessica Billar; REICHERT, Cadiele Oliana; COSTA, Renata Oliveira; LEVY, Debora; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, Juliana
- Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country(2022) LAGE, L. A. D. P. C.; BRITO, C. V.; BARRETO, G. C.; CULLER, H. F.; REICHERT, C. O.; LEVY, D.; COSTA, R. D. O.; ZERBINI, M. C. N.; ROCHA, V.; PEREIRA, J.Background: Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens. Methods: Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019. Results: With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P =.259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P =.018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P =.003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P =.0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P =.001), febrile neutropenia (70% vs. 38%, P =.003) and G3-4 thrombocytopenia (63% vs. 27%, P =.0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P =.05, as well as 2-year PFS (69.7% vs. 25.0%, P <.0001). In multivariate analysis, high LDH (HR 3.38, P =.007) was associated with decreased OS. CR at first line (HR: 0.09, P <.001) and consolidation with ASCT (HR: 0.08, P =.015) were predictors of increased OS. Conclusion: In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes. © 2022 Elsevier Inc.
- Whole Brain Radiotherapy Is an Effective and Safe Strategy to Consolidate Primary Central Nervous System Lymphoma Patients in Middle-Income Countries: A Real-Life Experience from Brazil(2022) LAGE, Luis Alberto de Padua Covas; SOARES, Vinicius Araujo; MENEGUIN, Thales Dalessandro; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; JACOMASSI, Mayara D'Auria; REIS, Diego Gomes Candido; ZERBINI, Maria Claudia Nogueira; COSTA, Renata Oliveira; ROCHA, Vanderson; PEREIRA, Juliana
- Patients with Sickle Cell Disease Treated with Hidroxiurea Have Higher Expression of PD-L1 in Monocytes(2022) GERVATAUSKAS, Kasys Meira; ROS, Felipe Augusto; FONSECA, Guilherme Henrique Hencklain; SILVA, Pedro Victor de Castro e; NOGUEIRA, Felipe Melo; OTSUKA, Liliana Suganuma; CARDOSO, Afonso Celso Almeida; GUALANDRO, Sandra Fatima Menosi; ROCHA, Vanderson; TOZATTO-MAIO, Karina
- The role of whole-brain radiotherapy (WBRT) in primary central nervous system lymphoma: is it an alternative to ASCT for consolidation following HD-methotrexate based induction in low-income settings?(2022) LAGE, Luis Alberto de Padua Covas; SOARES, Vinicius Araujo; MENEGUIN, Thales Dalessandro; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; JACOMASSI, Mayara D'Auria; REIS, Diego Gomes Candido; ZERBINI, Maria Claudia Nogueira; COSTA, Renata de Oliveira; ROCHA, Vanderson; PEREIRA, JulianaBackground Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Although potentially curable, its prognosis remains dismal. Its treatment is based on high-doses of methotrexate (HD-MTX) and rituximab, followed by consolidation therapy with whole-brain radiotherapy (WBRT) or autologous stem cell transplantation (ASCT). Currently, there is no consensus about the best consolidation strategy, but better outcomes with ASCT are obtained with conditioning regimens based on thiotepa, a high-cost drug with restricted use in resource-constrained settings. Latin American data on clinical outcomes, prognostic factors, and therapeutic management in PCNSL are virtually unknown. Methods This is a retrospective, observational, and single-center study involving 47-Brazilian patients with PCNSL. We aim to assess outcomes, determine predictors of survival, and compare responses, as well as toxicities in patients consolidated with chemotherapy alone versus chemotherapy plus WBRT. Results The median age at diagnosis was 59 years (24-88 years), and 53.1% were male. LDH >= UVN occurred in 44.7%, ECOG >= 2 in 67.6%, and 34.1% had multifocal disease. Hemiparesis was the main clinical presentation, observed in 55.3%, 51.0% had intermediate-/high-risk IELSG prognostic score, and 57.6% had an ABC-like phenotype by IHC. With a median follow-up of 24.4 months, estimated 5-year OS and PFS were 45.5% and 36.4%, respectively. Among 40 patients treated with HD-MTX-based induction, estimated 2-year OS was 85.8% for those consolidated with WBRT plus HIDAC versus only 41.5% for those consolidated with HIDAC alone (p < 0.001). Hematologic and non-hematologic toxicities were not significant, and severe cognitive impairment occurred in only 6.3% (3/47) of cases, all of them treated with WBRT. Age < 60 years, Hb >= 120 g/L and WBRT consolidation were associated with increased OS, however, LDH >= UVN, hypoalbuminemia, ECOG >= 2, Karnofsky PS < 70 and intermediate-/high-risk Barcelona score were associated with decreased OS. Conclusion Combined consolidation therapy (CCT) based on WBRT plus HIDAC was associated with increased OS in PCNSL compared to isolated consolidation therapy (ICT) based on HIDAC alone. Here, severe late neurotoxicity was uncommon with this approach. These data suggest that WBRT may be an effective and safe alternative to ASCT for consolidation therapy in PCNSL, particularly in resource-constrained settings, where access to thiotepa for pre-ASCT conditioning is not universal.
- Adrenal cysts of lymphatic origin: A clinical and pathological study of six cases and systematic literature review(2022) MARQUES-PIUBELLI, Mario L.; GONZALES, Eloiza Wilma Poma; GONCALVES, Victor Lucas; BALANCIN, Marcelo Luiz; BOTELHO, Maria Luiza A. A.; YAMAUCHI, Fernando Ide; ANDO, Sabrina de Mello; BRONDANI, Vania Balderrama; CHAMBO, Jose Luis; FRAGOSO, Maria Candida Barisson Villares; NOGUEIRA, Maria ClaudiaAdrenal cysts are rare, benign, and usually asymptomatic, being detected as an incidental finding on imaging methods. Adrenal Cysts of Lymphatic Origin (ACLO) and Adrenal Lymphangiomas (AL) are types of endothelial cyst and are the most prevalent subtype in this series. This study aims to present a single institutional experience of these rare cysts and compare their features with those found in the review of existing literature on ACLO and AL. Overall, thirteen cases of adrenal cysts were diagnosed and surgically excised during the study period, onto which we performed immunohistochemistry using a panel of antibodies (CD31, CD34, Pan Cytokeratin AE-1/AE3, Factor VII, D2-40, and ERG). Four cases of ACLO and two AL were found. The lesions predominantly affected right adrenal, and the majority of patients were middle-age females, of Caucasian ethnicity, and asymptomatic. In our literature review, we found 108 cases of ACLO/AL from 57 articles with similar sex and age distribution. The diagnosis and subclassification of adrenal cysts are challenging, and there is a significant overlapping between the definition of ACLO and AL.
- TET-2 mutations predict poor outcomes and are associated with unfavorable clinical-biological features in PTCL, not otherwise specified and angioimmunoblastic T-cell lymphoma in Brazilian patients(2022) LAGE, Luis Alberto de Padua Covas; BARRETO, Guilherme Carneiro; CULLER, Hebert Fabricio; CAVALCANTE, Jessica Billar; ALVES, Lucas Bassolli de Oliveira; NARDINELLI, Luciana; BENDIT, Israel; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, JulianaINTRODUCTION: Nodal peripheral T-cell lymphomas [nPTCL] constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation play a central role in their pathogenesis. However, the mutational landscape involving epigenetic regulators has never been reported in Latin American patients and their prognostic impact remains controversial. PATIENTS AND METHODS: From 2000 to 2019, 59-Brazilian patients with nPTCL were eligible for screening mutations in the IDH-1, IDH-2, RHOA, TET-2 and DNMT3A genes by Sanger sequencing at Formalin-Fixed Paraffin-Embedded samples [FFPE] of diagnosis. We reported the frequency, distribution and potential prognosis of these mutations. RESULTS: With a median follow-up of 3.70 years, estimate 2-year OS and PFS were 57.1% and 49.2%, respectively. Mutations in the IDH-1 gene were not found, mutations in the IDH-2 occurred in 3.4% (2/59), RHOA in 23.7% (14/59), TET-2 in 50.8% (30/59) and DNMT3A in 62.7% (37/59). RHOA gene mutations were more frequent in PTCL, NOS and AITL (p = 0.06). Almost half of the patients had more than one mutation in concomitance, particularly RHOA-mut and TET-2-mut. Mutations in RHOA (p = 0.030) and TET-2 (p = 0.046) were associated with high-tumor burden. In the non-ALCL subgroup (PTCL, NOS and AITL) TET-2 mutations were associated with decreased 2-year PFS [HR: 2.22, p = 0.048]. Likewise with lower overall response rate [ORR] (p = 0.048) and unfavorable clinical features, as bulky disease (p = 0.012), ECOG >= 2 (p = 0.032), B-symptoms (p = 0.012), >= 2 extranodal sites compromised (p = 0.022) and high-risk Prognostic Index for T-cell lymphoma (p = 0.005). CONCLUSION: Mutations in RHOA, TET-2 and DNMT3A were frequent in Brazilian patients with nPTCL. TET-2 mutations were associated with lower ORR for CHOP-like chemotherapy, decreased PFS and unfavorable clinical-biological characteristics in non-ALCL (PTCL, NOS and AITL). Further studies using a larger cohort may validate our findings.
- Diagnostic and prognostic implications of tumor expression of the GATA-3 gene in nodal peripheral T-cell lymphoma (nPTCL): Retrospective data from a Latin American cohort(2022) LAGE, Luis Alberto de Padua Covas; BRITO, Claudio Vinicius; LEVY, Debora; CULLER, Hebert Fabricio; COUTO, Samuel Campanelli Freitas; OLIVEIRA, Lucas Bassolli Alves de; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, JulianaBackground: Nodal peripheral T-cell lymphomas (nPTCL) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALKnegative. Their differential diagnosis and prognosis are an issue in clinical practice. Accurate biomarkers to define the different subtypes of nPTCL and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA-3 gene expression, and its capability to discriminate the different subtypes of nPTCL. Patients and methods: We retrospectively assessed GATA-3 gene expression by quantitative real time PCR (qRTPCR) from neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE) of 80 patients with nPTCL that were admitted in a single cancer treatment center from 2000 to 2017. Results: Median age was 49 years-old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years, 36.3% were classified as PTCL, NOS, 31.2% as ALK-negative ALCL, 21.2% as ALK-positive ALCL and 11.3% as AITL. The majority of cases had advanced stage cancer (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA-3 gene expression level