HELAINE LAIZ SILVA CHARCHAR
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
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- 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.
- A New Insight into the Surgical Treatment of Primary Macronodular Adrenal Hyperplasia(2020) TANNO, Fabio Yoshiaki; SROUGI, Victor; ALMEIDA, Madson Q.; YAMAUCHI, Fernando Ide; COELHO, Fernando Morbeck Almeida; NISHI, Mirian Yumie; ZERBINI, Maria Claudia Nogueira; SOARES, Iracy Silvia Correa; PEREIRA, Maria Adelaide Albergaria; CHARCHAR, Helaine Laiz Silva; LACOMBE, Amanda Meneses Ferreira; BRONDANI, Vania Balderrama; SROUGI, Miguel; NAHAS, Willian Carlos; MENDONCA, Berenice B.; CHAMBO, Jose Luis; FRAGOSO, Maria Candida Barisson VillaresPurpose: This prospective study presents the results of a new approach in the treatment of primary macronodular adrenal hyperplasia (PMAII), with simultaneous total adrenalectomy of the larger adrenal gland and partial adrenalectomy of the contralateral adrenal gland (adrenal-sparing surgery). Materials and Methods: We performed a prospective study including 17 patients with PMAH treated surgically with adrenal-sparing surgery in a tertiary referral hospital, with a median follow-up of 41 months. Clinical, hormonal, and genetic parameters were evaluated before surgery and during follow-up. All patients had at least 1 radiological examination before and after the procedure. Results: Among the 17 patients, all but 1 patient had complete hypercortisolism control, and 12 recovered normal adrenal function after surgery. Significant improvement in clinical parameters was observed: weight loss (P = .004); reduction of both systolic (P = .001) and diastolic (P = .001) blood pressure; and reduction in the number of antihypertensive drugs (P < .001). Intra-, peri-, and postoperative complications were not observed. Conclusion: Adrenal-sparing surgery is a safe and feasible procedure to treat patients with PMAH, providing a substantial chance of hypercortisolism control without the disadvantages of lifetime corticosteroid replacement. (C) Endocrine Society 2020.
- 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.
- Clinical spectrum of Li-Fraumeni syndrome/Li-Fraumeni-like syndrome in Brazilian individuals with the TP53 p.R337H mutation(2019) FERREIRA, Amanda Meneses; BRONDANI, Vania Balderrama; HELENA, Vanessa Petry; CHARCHAR, Helaine Laiz Silva; ZERBINI, Maria Claudia Nogueira; LEITE, Luiz Antonio Senna; HOFF, Ana Oliveira; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; DIZ, Maria Del Pilar Estevez; ALMEIDA, Madson Queiroz de; FRAGOSO, Maria Candida Barisson VillaresBackground: The TP53 p.R337H germline mutation is highly prevalent among children with adrenocortical tumors (ACTs) from South and Southeast Brazil. However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated. Patients and Methods: We investigated tumor profile data and outcomes of individuals and their close relatives with the TP53 p.R337H germline mutation. A questionnaire and the Toronto protocol were used for evaluation of asymptomatic carriers of this TP53 mutation. Results: The cohort of this study comprised 51 patients from 46 different families; 67% were female. All but one harbored the TP53 p.R337H mutation in heterozygous state; only one child was homozygous for this variant. Maternal allele inheritance occurred in 72% of the cases (p = 0,002). In pediatric group, ACT was the most common primary tumor at the diagnosis (55%; median age = 2 years). No patient of the pediatric group who initially presented with ACT developed a second primary tumor and 11% (n= 3) died due to complications related to the primary tumor (median follow-up time of 81.5 months, range = 3-378 months). In adult group, the main tumors at diagnosis were: adrenocortical carcinoma (ACC) (23%; median age= 29.5 years), breast cancer (12%; median age = 38.5 years), soft tissue sarcoma (8%; median age = 50.3 years) and choroid plexus carcinoma (CPC) (2%; median age= 18 years). Among adult patients who were diagnosed with ACC as the first primary tumor, all presented with aggressive disease as per histologic and clinical criteria at diagnosis, and 75% of patients died (median follow-up time of 19 months, range= 1-69 months). Five adult patients (22%) had a second primary tumor, including bronchoalveolar lung cancer (2 cases), ACC, uterine cervical carcinoma and fibrosarcoma. The diagnosis of these tumors was established from 8 to 36 months after the first primary tumor. Three families presented more than one case of ACT. Nine malignant neoplasms were diagnosed in asymptomatic carriers using Toronto protocol. Conclusions: This study confirms a high frequency of TP53 p.R337H mutation in pediatric group with ACT. In addition, we observed the occurrence of other tumors of LFS/LFL spectrum and a difference in the aggressiveness of ACTs depending on the age group in which they were diagnosed. The predominance of maternal mutated allele inheritance was first demonstrated in the affected Brazilian's families.
- Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules(2020) MARIANI, Beatriz Marinho de Paula; NISHI, Mirian Yumie; WANICHI, Ingrid Quevedo; BRONDANI, Vania Balderrama; LACOMBE, Amanda Meneses Ferreira; CHARCHAR, Helaine; PEREIRA, Maria Adelaide Albergaria; SROUGI, Victor; TANNO, Fabio Yoshiaki; CECCATO, Filippo; REGAZZO, Daniela; BARBOT, Mattia; OCCHI, Gianluca; ALBIGER, Nora Maria Elvira; VIEIRA-CORREA, Marcelo; KATER, Claudio Elias; SCARONI, Carla; CHAMBO, Jose Luis; ZERBINI, Maria Claudia Nogueira; MENDONCA, Berenice B.; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida Barisson VillaresObjective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.
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