IBERE CAUDURO SOARES
Índice h a partir de 2011
10
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
20 resultados
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- Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma(2021) TOYOSHIMA, Marcos Tadashi Kakitani; DOMINGUES, Regina Barros; SOARES, Ibere Cauduro; DANILOVIC, Debora Lucia Seguro; AMORIM, Larissa Costa; CAVALCANTE, Edla R. C.; ANTONACIO, Fernanda F.; ROITBERG, Felipe Santa Rosa; HOFF, Ana OliveiraCollision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient ' s death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.
- 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.
- PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without beta-catenin mutations(2011) CANI, Carolina M. G.; MATUSHITA, Hamilton; CARVALHO, Luciani R. S.; SOARES, Ibere C.; BRITO, Luciana P.; ALMEIDA, Madson Q.; MENDONCA, Berenice B.INTRODUCTION: Activating mutations in exon 3 of the beta-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between beta-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. OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the beta-catenin gene was screened for mutations, and the expression of the beta-catenin gene and PROP1 was evaluated. METHODS: The beta-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and beta-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and beta-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the beta-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of beta-catenin gene overexpression was found in 71% of the tumors with beta-catenin mutations and in 40% of the tumors without mutations, and beta-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of beta-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear beta-catenin staining pattern regardless of the presence of a beta-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.
- Rebmab200, a Humanized Monoclonal Antibody Targeting the Sodium Phosphate Transporter NaPi2b Displays Strong Immune Mediated Cytotoxicity against Cancer: A Novel Reagent for Targeted Antibody Therapy of Cancer(2013) SANTOS, Mariana Lopes dos; YEDA, Fernanda Perez; TSURUTA, Lilian Rumi; HORTA, Bruno Brasil; PIMENTA JR., Alecio A.; DEGAKI, Theri Leica; SOARES, Ibere C.; TUMA, Maria Carolina; OKAMOTO, Oswaldo Keith; ALVES, Venancio A. F.; OLD, Lloyd J.; RITTER, Gerd; MORO, Ana MariaNaPi2b, a sodium-dependent phosphate transporter, is highly expressed in ovarian carcinomas and is recognized by the murine monoclonal antibody MX35. The antibody had shown excellent targeting to ovarian cancer in several early phase clinical trials but being murine the antibody's full therapeutic potential could not be explored. To overcome this impediment we developed a humanized antibody version named Rebmab200, expressed in human PER.C6 (R) cells and cloned by limiting dilution. In order to select a clone with high therapeutic potential clones were characterized using a series of physicochemical assays, flow cytometry, real-time surface plasmon resonance, glycosylation analyses, immunohistochemistry, antibody-dependent cell-mediated cytotoxicity, complement-dependent-cytotoxicity assays and quantitative PCR. Comparative analyses of Rebmab200 and MX35 monoclonal antibodies demonstrated that the two antibodies had similar specificity for NaPi2b by flow cytometry with a panel of 30 cell lines and maintained similar kinetic parameters. Robust and high producer cell clones potentially suitable for use in manufacturing were obtained. Rebmab200 antibodies were assessed by immunohistochemistry using a large panel of tissues including human carcinomas of ovarian, lung, kidney and breast origin. An assessment of its binding towards 33 normal human organs was performed as well. Rebmab200 showed selected strong reactivity with the tested tumor types but little or no reactivity with the normal tissues tested confirming its potential for targeted therapeutics strategies. The remarkable cytotoxicity shown by Rebmab200 in OVCAR-3 cells is a significant addition to the traits of stability and productivity displayed by the top clones of Rebmab200. Antibody-dependent cell-mediated toxicity functionality was confirmed in repeated assays using cancer cell lines derived from ovary, kidney and lung as targets. To explore use of this antibody in clinical trials, GMP production of Rebmab200 has been initiated. As the next step of development, Phase I clinical trials are now planned for translation of Rebmab200 into the clinic.
- Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes(2022) PAVANELLI, Ana Carolina; MANGONE, Flavia Rotea; YOGANATHAN, Piriya; BESSA, Simone Aparecida; NONOGAKI, Suely; OSORIO, Cynthia A. B. de Toledo; ANDRADE, Victor Piana de; SOARES, Ibere Cauduro; MELLO, Evandro Sobrosa de; MULLIGAN, Lois M.; NAGAI, Maria AparecidaPurpose Breast cancer (BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance. Methods Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays (TMAs) containing a cohort of 361 Luminal subtype BC. Results Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015). Conclusion Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC.
- Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?(2020) DANILOVIC, Debora L. S.; CASTRONEVES, Luciana A.; SUEMOTO, Claudia K.; ELIAS, Livia O.; SOARES, Ibere C.; CAMARGO, Rosalinda Y.; CORREA, Fernanda A.; HOFF, Ana O.; MARUI, SuemiBackground: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.
- Epstein-Barr Virus and PD-L1 in Esophageal and Esophagogastric Junction Cancer: Differences According to Location and Histological Type(2022) RIBEIRO, Mateus Barradas; MARQUES, Sergio Barbosa; SOARES, Ibere Cauduro; PEREIRA, Marina Alessandra; TAKEDA, Flavio Roberto; SAFATLE-RIBEIRO, Adriana Vaz; JR, Ulysses Ribeiro
- Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma(2020) LACOMBE, Amanda Meneses Ferreira; SOARES, Ibere Cauduro; MARIANI, Beatriz Marinho de Paula; NISHI, Mirian Yumie; BEZERRA-NETO, Joao Evangelista; CHARCHAR, Helaine da Silva; BRONDANI, Vania Balderrama; TANNO, Fabio; SROUGI, Victor; CHAMBO, Jose Luiz; FREITAS, Ricardo Miguel Costa de; MENDONCA, Berenice Bilharinho; HOFF, Ana O.; ALMEIDA, Madson Q.; WEIGAND, Isabel; KROISS, Matthias; ZERBINI, Maria Claudia Nogueira; FRAGOSO, Maria Candida Barisson VillaresAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score >= 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0-4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score <= 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26-3.66; p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.
- High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53(2020) BRONDANI, Vania Balderrama; MONTENEGRO, Luciana; LACOMBE, Amanda Meneses Ferreira; MAGALHAES, Breno Marchiori; NISHI, Mirian Yumie; FUNARI, Mariana Ferreira de Assis; NARCIZO, Amanda de Moraes; CARDOSO, Lais Cavalca; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; DENES, Francisco Tibor; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; ALMEIDA, Madson Queiroz; LERARIO, Antonio Marcondes; SOARES, Ibere Cauduro; FRAGOSO, Maria Candida Barisson VillaresAdrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for theMMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of alteredMMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.
- Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer(2015) FARIA, Andre M.; SBIERA, Silviu; RIBEIRO, Tamaya C.; SOARES, Ibere C.; MARIANI, Beatriz M. P.; FREIRE, Daniel S.; SOUSA, Gabriela R. V. de; LERARIO, Antonio M.; RONCHI, Cristina L.; DEUTSCHBEIN, Timo; WAKAMATSU, Alda; ALVES, Venancio A. F.; ZERBINI, Maria Claudia N.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; FASSNACHT, Martin; ALMEIDA, Madson Q.ObjectiveLIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs). Patients and methodsLIN28 protein expression was assessed in 266 adults ACTs (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN28A and LIN28B gene expression was analysed in 59 ACTs (31 adenomas and 28 carcinomas) and copy number variation in 39 ACTs. In addition, we determined the expression of let-7 family, mir-9, mir-30 and mir-125 in 28 carcinomas. ResultsLIN28A gene was overexpressed in aggressive ACCs when compared with adenomas and nonaggressive ACCs, but no LIN28A copy number variation was found in ACTs. Unexpectedly, weak LIN28 protein expression was significantly associated with reduced disease-free survival in ACC patients (P=001), but for overall survival only a trend was detectable (P=0117). In the multivariate analysis, only Ki67 index 10% (HR 46, P=0000) and weak LIN28 protein expression (HR 20, P=003) were independent predictors of recurrence in ACC patients. Interestingly, mir-9 expression, a negative LIN28A/B regulator, was significantly higher in aggressive than in nonaggressive ACCs [2076 (from 36 to 9307) vs 1334 (from 24 to 5193); P=0011] and was highly associated with reduced overall (P=001) and disease-free survival (P=001). However, mir-9 prognostic role should be further evaluated in a larger cohort. ConclusionWeak LIN28 protein expression was associated with recurrence in ACCs. Additionally, overexpression of mir-9, a negative LIN28A regulator, was associated with poor outcome.