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1.
Eur J Endocrinol ; 191(1): 64-74, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38924056

RESUMO

OBJECTIVE: Pediatric adrenocortical carcinoma (pACC) is rare, and prognostic stratification remains challenging. We aimed to confirm the prognostic value of the previously published pediatric scoring system (pS-GRAS) in an international multicenter cohort. DESIGN: Analysis of pS-GRAS items of pACC from 6 countries in collaboration of ENSAT-PACT, GPOH-MET, and IC-PACT. METHODS: We received patient data of the pS-GRAS items including survival information from 9 centers. PS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index: 0%-9% = 0; 10%-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX/R1/R2 = 1 point), age (<4 years = 0; ≥4 years = 1 point), and hormone production (androgen production = 0; glucocorticoid-/mixed-/no-hormone production = 1 point) generating 8 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-7). Primary endpoint was overall survival (OS). RESULTS: We included 268 patients with median age of 4 years. The analysis of the pS-GRAS score showed a significantly favorable prognosis in patients with a lower scoring compared to higher scoring groups (5-year OS: Group 1 98%; group 2 87% [hazard ratio {HR} of death 3.6, 95% CI of HR 1.6-8.2]; group 3 43% [HR of death 2.8, 95% CI 1.9-4.4]; group 4: OS 18% [HR of death 2.1, 95% CI 1.7-2.7]). In the multivariable analysis, age (HR of death 3.5, 95% CI 1.8-7.0), resection status (HR of death 5.5, 95% CI 2.7-11.1), tumor stage (HR of death 1.9, 95% CI of HR 1.2-3.0), and Ki67 index (HR of death 1.7, 95% CI 1.2-2.4) remained strong independent outcome predictors. Especially infants < 4 years showed more often low-risk constellations with a better OS for all tumor stages. CONCLUSION: In an international multicenter study, we confirmed that the pS-GRAS score is strongly associated with overall survival among patients with pACC. Age, resection status, stage, and Ki67 index are important parameters for risk stratification.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Masculino , Feminino , Prognóstico , Criança , Pré-Escolar , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/patologia , Adolescente , Lactente , Estudos de Coortes , Estadiamento de Neoplasias
2.
Cancers (Basel) ; 12(3)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183347

RESUMO

The SF-1 transcription factor target gene FATE1 encodes a cancer-testis antigen that has an important role in regulating apoptosis and response to chemotherapy in adrenocortical carcinoma (ACC) cells. Autoantibodies directed against FATE1 were previously detected in patients with hepatocellular carcinoma. In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.

3.
Br J Cancer ; 122(8): 1231-1241, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32147670

RESUMO

BACKGROUND: Genome-wide association studies (GWASs) have enriched the fields of genomics and drug development. Adrenocortical carcinoma (ACC) is a rare cancer with a bimodal age distribution and inadequate treatment options. Paediatric ACC is frequently associated with TP53 mutations, with particularly high incidence in Southern Brazil due to the TP53 p.R337H (R337H) germline mutation. The heterogeneous risk among carriers suggests other genetic modifiers could exist. METHODS: We analysed clinical, genotype and gene expression data derived from paediatric ACC, R337H carriers, and adult ACC patients. We restricted our analyses to single nucleotide polymorphisms (SNPs) previously identified in GWASs to associate with disease or human traits. RESULTS: A SNP, rs971074, in the alcohol dehydrogenase 7 gene significantly and reproducibly associated with allelic differences in ACC age-of-onset in both cohorts. Patients homozygous for the minor allele were diagnosed up to 16 years earlier. This SNP resides in a gene involved in the retinoic acid (RA) pathway and patients with differing levels of RA pathway gene expression in their tumours associate with differential ACC progression. CONCLUSIONS: These results identify a novel genetic component to ACC development that resides in the retinoic acid pathway, thereby informing strategies to develop management, preventive and therapeutic treatments for ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Genes p53 , Polimorfismo de Nucleotídeo Único , Tretinoína/fisiologia , Adolescente , Neoplasias do Córtex Suprarrenal/epidemiologia , Carcinoma Adrenocortical/epidemiologia , Fatores Etários , Idade de Início , Álcool Desidrogenase/genética , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Lactente , Masculino
4.
Cancers (Basel) ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694270

RESUMO

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.

5.
J Pediatr Hematol Oncol ; 28(2): 82-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16462579

RESUMO

The authors report on the incidence and clinical characteristics of neuroblastoma in southern Brazil. The aims of the study were to evaluate the age at diagnosis, tumor stage, MYCN status, and tumor histopathology, and to relate these factors to survival. All patients with neuroblastoma, 15 years old or younger (n = 125), admitted to the three major pediatric oncology hospitals in the state of Parana over a period of 11 years (between January 1990 and December 2000), were included in the analysis. All patients were followed for at least 5 years. In addition, a FISH evaluation for MYCN status was conducted in a subset of 34 tumors. Overall survival for tumor stages 1, 2, 3, and 4 was 100%, 72%, 59%, and 17%, respectively. Sixty-two percent (77/125) of all patients were older than 2 years; these represented 71% (57/80) of the patients with stage 4 disease. Children who presented with an unfavorable histopathology had a significantly worse prognosis (20% survival) than children with a favorable histopathology (67% survival). MYCN amplification was detected most commonly in stages 3 and 4 tumors (13/16). These data showed a delayed diagnosis of neuroblastoma in children in southern Brazil, and consequently survival was considerably lower in these patients.


Assuntos
Neuroblastoma/epidemiologia , Adolescente , Idade de Início , Brasil/epidemiologia , Criança , Pré-Escolar , Terapia Combinada , Diagnóstico Precoce , Feminino , Genes myc , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/terapia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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