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1.
Medicine (Baltimore) ; 99(40): e22620, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019484

RESUMO

RATIONALE: Low-dose mitotane has been widely used for many decades in patients with advanced adrenocortical carcinoma (ACC), which exhibited good safety profiles compared with the high-dose regimen. The clinical efficacy and toxicity of mitotane are closely related to its plasma concentration, and therapeutic drug monitoring (TDM) is recommended. Until now, no severe adverse drug reaction (ADR) related to the toxic plasma level after a short-term treatment of low-dose mitotane has been published. PATIENT CONCERNS: A 50-year-old Chinese female presented with severe neurological adverse events related to a toxic plasma levels of 42.8 mg/L after 4 months treatment of low-dose mitotane. DIAGNOSES: During the course of therapy, no other medication could cause neurological adverse events. Therefore, we suspected a high sensitivity to the side effect of mitotane related to a toxic plasma level. INTERVENTIONS: Treatment of mitotane was stopped. OUTCOMES: The trough plasma concentration of mitotane decreased to 18.7 mg/mL after one and a half months, and the neurological symptoms gradually improved after drug discontinuance. LESSONS: The present case provides the first report of severe neurological adverse events induced by the short-term use of low-dose mitotane for adjuvant treatment in a patient with ACC, indicating that potentially severe ADR can also occur when using low-dose regimen in the early stage of treatment. TDM and early recognition could result in a favorable outcome.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/toxicidade , Mitotano/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Mitotano/sangue , Mitotano/uso terapêutico , Síndromes Neurotóxicas , Resultado do Tratamento , Suspensão de Tratamento
2.
PLoS One ; 15(4): e0231665, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287321

RESUMO

BACKGROUND: Many genomic analyses of cortisol-producing adrenocortical carcinoma (ACC) have been reported, but very few have come from East Asia. The first objective of this study is to verify the genetic difference with the previous reports by analyzing targeted deep sequencing of 7 Japanese ACC cases using next-generation sequencing (NGS). The second objective is to compare the somatic variant findings identified by NGS analysis with clinical and pathological findings, aiming to acquire new knowledge about the factors that contribute to the poor prognosis of ACC and to find new targets for the treatment of ACC. METHOD: DNA was extracted from ACC tissue of seven patients and two reference blood samples. Targeted deep sequencing was performed using the MiSeq system for 12 genes, and the obtained results were analyzed using MuTect2. The hypothesis was obtained by integrating the somatic variant findings with clinical and pathological data, and it was further verified using The Cancer Genome Atlas (TCGA) dataset for ACC. RESULTS: Six possible pathogenic and one uncertain significance somatic variants including a novel PRKAR1A (NM_002734.4):c.545C>A (p.T182K) variant were found in five of seven cases. By integrating these data with pathological findings, we hypothesized that cases with TP53 variants were more likely to show atypical mitotic figures. Using TCGA dataset, we found that atypical mitotic figures were associated with TP53 somatic variant, and mRNA expression of CCNB2 and AURKA was significantly high in TP53 mutated cases and atypical mitotic figure cases. CONCLUSION: We believe this is the first report that discusses the relationship between atypical mitotic figures and TP53 somatic variant in ACC. We presumed that overexpression of CCNB2 and AURKA mRNA may cause atypical mitosis in TP53 somatic mutated cases. Because AURKA is highly expressed in atypical mitotic cases, it may be an appropriate indicator for AURKA inhibitors.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Aurora Quinase A/genética , Ciclina B2/genética , Mitose , Regulação para Cima , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Aurora Quinase A/metabolismo , Ciclina B2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/genética
4.
Surgery ; 167(2): 352-357, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31272813

RESUMO

BACKGROUND: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy. METHODS: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis. RESULTS: In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P = .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P = .008). Margin status at metachronous metastasectomy was not associated with survival (P = .452). CONCLUSION: Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/secundário , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Estados Unidos/epidemiologia
5.
Pediatr Blood Cancer ; 67(2): e28086, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31738008

RESUMO

INTRODUCTION: Pediatric adrenal cortical tumors are characterized by a wide spectrum of behavior. Questions remain regarding intermediate disease stages with isolated tumor rupture or relapse. OBJECTIVES: To describe clinical characteristics, treatment strategy, and outcome of patients depending on disease stage, tumor rupture, or in case of a refractory tumor, to discuss optimal management. MATERIAL AND METHODS: Pediatric patients with histological material reviewed and treated between 2000 and 2018 in 23 French oncology centers were included. RESULTS: Among 95 cases, 59% of patients had stage I tumors (n = 55), 16% had stage II tumors (n = 16), 19% had stage III tumors (n = 17), and 5% had stage IV tumors (n = 5) (missing data: 2). Overall, 27% of patients (n = 25) had an unfavorable histology. Initial tumor resection was performed for 90% of patients (n = 86). Systemic therapies included mitotane in 20 cases and chemotherapy in 13 cases. Among 17 stage III patients, 12 had microscopic residual tumor due to an initial biopsy (n = 5), intraoperative rupture (n = 8), or surgical resection with microscopic residue or tumor spillage surgery (n = 1) (two patients with two modalities). After a median follow-up of 96 months (25-119), four early progressions and two relapses occurred. A total of seven patients died, including five of disease. Stage III diseases due to microscopic residual disease correlated with a worse prognosis: 5-year progression-free survival 44% (95% CI, 22-87%) versus 82% (95% CI, 73-91%) for the whole cohort (P < .0001). Among the 14 patients with refractory disease, only 3 were alive and free of disease after multimodal second-line therapy. CONCLUSIONS: Stage III diseases due to a microscopic residual tumor have a dismal prognosis, arguing for the systematic use of adjuvant therapy. Patients with a relapsed disease should be included in experimental studies.


Assuntos
Neoplasias do Córtex Suprarrenal/classificação , Neoplasias do Córtex Suprarrenal/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Terapia de Salvação , Adolescente , Neoplasias do Córtex Suprarrenal/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
AJR Am J Roentgenol ; 214(2): 390-394, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31691613

RESUMO

OBJECTIVE. The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this information may inform guidelines for diagnosis and management of ACC. MATERIALS AND METHODS. A comprehensive search of databases of published studies was performed. Two reviewers independently selected original research, case series, or case reports of ACC with macroscopic fat on imaging and extracted data. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS. Three case reports and one retrospective study comprising a total of seven cases of ACC (lesion size: range, 6.5-22 cm) with macroscopic fat were included. ACC was symptomatic in all patients; neither locally invasive features nor metastases were reported. Four cases had less than 5% macroscopic fat on imaging, and the percentage fat on imaging was not reported for the remaining three cases. With regard to the risk of bias, one case had high risk for the index test domain because of potentially unreliable determination of macroscopic fat (i.e., no pathologic confirmation). All seven cases (from four studies) had unclear risk for the reference standard domain because there was insufficient information about the reference standard to determine whether ACC was correctly diagnosed. All studies were at low risk of bias in the flow and timing domain. CONCLUSION. There are few reports of macroscopic fat in ACC detected on imaging studies; among the reports of macroscopic fat in ACC, tumors were large (> 6 cm) and had a small proportion of gross fat (< 5%). The reliability of reported cases is questionable primarily because of insufficient details about pathologic diagnosis. Based on this information, a change in guideline recommendations may not be warranted. However, consideration of follow-up or biopsy of patients with large symptomatic tumors (> 6 cm) containing a small proportion of fat (< 5%) may be appropriate.


Assuntos
Tecido Adiposo/patologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Tecido Adiposo/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Carcinoma Adrenocortical/diagnóstico por imagem , Humanos
7.
Surgery ; 167(1): 224-232, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31522749

RESUMO

BACKGROUND: Adrenocortical carcinoma is an aggressive malignancy with a low but variable overall survival rate. The role of in adrenocortical carcinoma is poorly understood. Thus, in this study we performed long noncoding RNA expression profiling in adrenocortical carcinomas, adrenocortical adenomas, and normal adrenal cortex. METHODS: Long noncoding RNA expression profile using Human LncRNA/mRNA Expression Microarray V3.0 (Arraystar, Inc, Rockville, MD) was analyzed in samples from 11 adrenocortical adenomas, 9 adrenocortical carcinomas, and 5 normal adrenal cortex. Differentially expressed long noncoding RNAs were validated using TaqMan, real-time quantitative polymerase chain reaction with additional samples. The dataset from the adrenocortical carcinoma Cancer Genome Atlas Programproject was used to evaluate the prognostic utility of long noncoding RNAs. RESULTS: Unsupervised hierarchical clustering showed distinct clustering of adrenocortical carcinoma samples compared with normal adrenal cortex and adrenocortical adenoma samples by long noncoding RNA expression profiles. A total of 874 long noncoding RNAs were differentially expressed between adrenocortical carcinoma and normal adrenal cortex. LINC00271 expression level was associated with prognosis, patients with low LINC00271 expression survived a shorter time than patients with high LINC00271 expression. Low LINC00271 expression was positively associated with WNT signaling, cell cycle, and chromosome segregation pathways. CONCLUSION: Adrenocortical carcinoma has a distinct long noncoding RNA expression profile. LINC00271 is downregulated in adrenocortical carcinoma and appears to be involved in biologic pathways commonly dysregulated in adrenocortical carcinoma.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Segregação de Cromossomos/genética , Variações do Número de Cópias de DNA , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Via de Sinalização Wnt/genética
8.
Surgery ; 167(1): 216-223, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31543320

RESUMO

BACKGROUND: While roughly half of adrenocortical carcinomas are functional, whether functional status impacts outcomes remains controversial. We compared presentation and survival for functional and nonfunctional neoplasms. METHODS: Adult patients presented with adrenocortical carcinomas at the Mayo Clinic were included. Tumor characteristics and outcomes were analyzed. RESULTS: The 266 identified patients presented with stage I (6%), II (33%), III (26%), and IV disease (32%); stage was unknown in 3%. Fifty-three percent of tumors were functional; patients with functional adrenocortical carcinomas were younger, more likely to be female, and more likely to present with metastatic disease. Surgical resection was undertaken in 84% of patients with 69% having R0 resection. While 30-day morbidity was similar between functional and nonfunctional adrenocortical carcinomas, median overall survival was better for nonfunctional adrenocortical carcinomas (median 66 vs 22 months, P = .01). Functional adrenocortical carcinomas was independently associated with shorter survival after adjusting for age, sex, grade, stage, and resection attempt: hazard ratio = 1.5 (95% confidence interval, 1.04-2.14, P = .03). CONCLUSION: In our cohort, long term survival was worse for all patients with functional tumors. However, when analyzing patients with R0 resection, there was no survival difference between functional and nonfunctional adrenocortical carcinomas, signaling need for better understanding of adrenocortical carcinomas behavior to individualize and optimize treatment strategies.


Assuntos
Corticosteroides/metabolismo , Neoplasias do Córtex Suprarrenal/mortalidade , Córtex Suprarrenal/patologia , Adrenalectomia , Carcinoma Adrenocortical/mortalidade , Adolescente , Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
Surgery ; 167(1): 233-240, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561992

RESUMO

INTRODUCTION: Adrenocortical carcinoma is an aggressive cancer with a poor prognosis. Long noncoding RNAs are differentially expressed in cancer patients and contribute to cellular homeostasis, survival, and metastasis. We hypothesize that our novel C-terminal Hsp90 inhibitor KU758 can effectively target adrenocortical carcinoma cells and favorably alter long noncoding RNA expression. METHODS: Cell viability after KU758 treatment was measured in the adrenocortical carcinoma cell lines SW13, RL251, and NCI-H295R by MTS assay. Cellular mobility and metastatic potential after Hsp90 inhibition was measured through migration, invasion, and aggregate formation assays. ß-catenin activity in NCI-H295R cells was determined by immunofluorescence and polymerase chain reaction. Long noncoding RNA expression was determined by polymerase chain reaction array after Hsp90 inhibition. RESULTS: KU758 is selective for adrenocortical carcinoma cells with IC50 values of 0.6 to 2.4 µM. KU758 treatment can effectively reduce migration, invasion, and aggregate formation in NCI-H295R and SW13 cells. ß-catenin activity is decreased after treatment with KU758. Treatment with KU758 is associated with overall statistically significant upregulation of long noncoding RNA expression, including the tumor suppressor GAS5, which is implicated in the ß-catenin and mammalian target of rapamycin pathways in adrenocortical carcinoma. CONCLUSION: The novel C-terminal Hsp90 inhibitor KU758 is effective in the treatment of adrenocortical carcinoma cells and can significantly alter long noncoding RNA expression for tumor suppression.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Concentração Inibidora 50 , Regulação para Cima/efeitos dos fármacos
10.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513709

RESUMO

CONTEXT: Although the development of immune checkpoint inhibitors has transformed treatment strategies of several human malignancies, research models to study immunotherapy in adrenocortical carcinoma (ACC) are lacking. OBJECTIVE: To explore the effect of anti-PD1 immunotherapy on the alteration of the immune milieu in ACC in a newly generated preclinical model and correlate with the response of the matched patient. DESIGN, SETTING, AND INTERVENTION: To characterize the CU-ACC2-M2B patient-derived xenograft in a humanized mouse model, evaluate the effect of a PD-1 inhibitor therapy, and compare it with the CU-ACC2 patient with metastatic disease. RESULTS: Characterization of the CU-ACC2-humanized cord blood-BALB/c-Rag2nullIl2rγnullSirpaNOD model confirmed ACC origin and match with the original human tumor. Treatment of the mice with pembrolizumab demonstrated significant tumor growth inhibition (60%) compared with controls, which correlated with increased tumor infiltrating lymphocyte activity, with an increase of human CD8+ T cells (P < 0.05), HLA-DR+ T cells (P < 0.05) as well as Granzyme B+ CD8+ T cells (<0.001). In parallel, treatment of the CU-ACC2 patient, who had progressive disease, demonstrated a partial response with 79% to 100% reduction in the size of target lesions, and no new sites of metastasis. Pretreatment analysis of the patient's metastatic liver lesion demonstrated abundant intratumoral CD8+ T cells by immunohistochemistry. CONCLUSIONS: Our study reports the first humanized ACC patient-derived xenograft mouse model, which may be useful to define mechanisms and biomarkers of response and resistance to immune-based therapies, to ultimately provide more personalized care for patients with ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Modelos Animais de Doenças , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Neoplasias do Córtex Suprarrenal/imunologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/imunologia , Carcinoma Adrenocortical/patologia , Animais , Antineoplásicos Imunológicos/farmacologia , Apoptose , Proliferação de Células , Feminino , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptor de Morte Celular Programada 1/imunologia , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Medicine (Baltimore) ; 98(49): e18259, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804360

RESUMO

RATIONALE: Adrenocortical carcinoma is a rare aggressive type of cancer whose prognosis is poor, particularly for metastatic entities. Metastatic adrenocortical carcinoma in the spine is a rare disease with no standard curative managements yet. The objective of this study is to report a very rare case of spinal metastases of adrenocortical carcinoma successfully managed by combination of cement augmentation, radiotherapy together with adjuvant programmed cell death 1 (PD-1) therapy. The management of these unique cases has yet to be well-documented. PATIENT CONCERNS: A 42-year-old woman presented with a 3-month history of continuous and progressive back pain. The patient, who had been diagnosed of right pheochromocytoma, received surgical treatment of right adrenalectomy 14 months ago in another hospital, followed by no further treatment. DIAGNOSIS: Magnetic resonance imaging of spine showed vertebral pathological fracture of L1, spinal cord compression secondary to the epidural component of the L1 mass, with increased metastatic marrow infiltration of the right L1 vertebral body, which presented as a solid tumor. Postoperative pathology confirmed the diagnosis of spinal metastases of adrenocortical carcinoma. INTERVENTIONS: The patient underwent cement augmentation via a posterior approach, radiotherapy, radiofrequency ablation of psoas major muscle occupying lesions, right chest wall, liver and kidney recess together with adjuvant PD-1 therapy. OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 6-month and 1-year follow-up visit. There were no complications associated with the operation during the follow-up period. LESSONS: Combined efforts of specialists from orthopedics, urology, interventional radiology, radiotherapy, pathology, endocrinology, and medical oncology led to the successful diagnosis and management of this patient. Metastatic adrenocortical carcinoma of the spine, although rare, should be part of the differential diagnosis when the patient has a history of adrenal carcinoma and presents with back pain, myelopathy, or radiculopathy. We recommend the posterior approach for total excision of the spinal metastatic adrenocortical carcinoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation, radiotherapy, and targeted PD-1 therapy may also be good choices for treatment.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/secundário , Carcinoma Adrenocortical/terapia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adulto , Terapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética
12.
BMC Cancer ; 19(1): 1165, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783819

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs. METHODS: Clinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1. RESULTS: FSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC. CONCLUSIONS: These results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Proteínas de Transporte/metabolismo , Proteína Forkhead Box M1/metabolismo , Proteínas dos Microfilamentos/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/imunologia , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/imunologia , Carcinoma Adrenocortical/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação para Cima , Adulto Jovem
13.
Ann Endocrinol (Paris) ; 80(5-6): 308-313, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31722787

RESUMO

Compared to benign adrenal lesions, secreting or otherwise, malignant adrenocortical carcinoma is rare. Overall prognosis is poor, with <50% 5-year survival. Various prognostic factors have been identified, some tumor-related and others directly linked to surgical treatment. Surgery is the only possible curative treatment, and is decided upon in a multidisciplinary medical-surgical team meeting. Surgical approach (laparotomy vs. laparoscopy) remains a matter of debate. In the light of a recent literature search, the present review reassesses the prognostic criteria of surgical resection, the quality of which determines overall and recurrence-free survival.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Resultado do Tratamento , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Humanos , Laparoscopia , Laparotomia , Excisão de Linfonodo , Metástase Linfática/patologia , Margens de Excisão , Recidiva Local de Neoplasia/terapia , Taxa de Sobrevida
14.
J Surg Oncol ; 120(8): 1450-1455, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31733070

RESUMO

BACKGROUND: Recurrent adrenocortical carcinoma (ACC) has a poor prognosis with minimal clinical and biochemical factors to guide management. The aim of this study was to evaluate the prognostic significance of systemic inflammatory response in patients with recurrent ACC. METHODS: Patients who underwent resection for recurrent ACC were retrospectively analyzed. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), and mean platelet volume were calculated. RESULTS: Twenty-five patients (age at operation 52.2 ± 9.5 years) were identified. We observed a statistically significant shorter disease-specific survival (DSS) in patients with LMR less than 4 (41 ± 7.4 months vs 71 ± 12.3, P = .023) and male sex (26.6 ± 4.2 months vs 57.6 ± 9.5 months, P = .079), while time-to-recurrence (TTR) less than 12 months (40 ± 7.7 months vs 70.3 ± 13.1 months, P = .059) had a trend on univariate analysis for worse DSS. On multivariable analysis, LMR < 4 (hazard ratio [HR] 4.18; 95% confidence interval [CI]: 1.18-14.76; P = .027) and TTR less than 12 months (HR 2.77 95% CI: 1-7.62; P = .049) were found to be significantly associated with worse DSS. CONCLUSION: Preoperative LMR greater than 4 and TTR greater than 12 months are associated with longer DSS. Patients with LMR greater than 4 and TTR greater than 12 months may benefit from a more aggressive therapeutic approach and may require less frequent surveillance.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/mortalidade , Contagem de Linfócitos , Monócitos/metabolismo , Recidiva Local de Neoplasia/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Adulto , Biomarcadores/sangue , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
15.
Ann Endocrinol (Paris) ; 80(5-6): 324-328, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31703800

RESUMO

AIM: Some resected adrenal-confined adrenocortical carcinomas metastasize and others not. The present study was designed to evaluate the expression of metallothionein protein (MT) and minichromosome maintenance protein-2 (MCM2) in adrenocortical carcinomas and adrenocortical adenomas, and to test the correlation between this and adrenocortical carcinoma aggressiveness. MATERIALS AND METHODS: The study comprised 14 patients operated on for adrenocortical carcinoma, 15 operated on for adrenocortical adenoma and 2 with normal adrenals. Hematoxylin-eosin staining was used for histological evaluation under light microscopy, and sequential sections were used for MCM2 and MT staining. RESULTS: In normal adrenals, positive staining was weak for MT and zero for MCM2. Rates of positive staining for MT and MCM2 were significantly higher in adrenocortical carcinomas than in adrenocortical adenomas (P=0.008 and P<0.001, respectively). In adrenocortical carcinomas, a significant positive correlation was found between MCM2 staining and Weiss revisited score (P=0.022) but not for Weiss score, and a significant positive correlation was found between MCM2 and mitotic rate on histology (P=0.033). MCM2 but not MT staining was also shown to correlate significantly with stage IV carcinoma (P=0.008 and P=0.165, respectively). CONCLUSION: MCM2 and MT are overexpressed in adrenocortical carcinoma, and MCM2 expression correlates significantly with metastatic disease.


Assuntos
Neoplasias do Córtex Suprarrenal/química , Adenoma Adrenocortical/química , Carcinoma Adrenocortical/química , Metalotioneína/análise , Componente 2 do Complexo de Manutenção de Minicromossomo/análise , Neoplasias do Córtex Suprarrenal/patologia , Glândulas Suprarrenais/química , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estudos Retrospectivos
16.
Medicine (Baltimore) ; 98(46): e17921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725643

RESUMO

The aim of the study was to investigate the molecular mechanisms in childhood adrenocortical tumors (ACTs), which is still unclear.A total of 9 girls and 4 boys with ACTs were enrolled. Relevant clinical features were obtained from records. Immunohistochemistry of vimentin, chromogranin A, S100, synaptophysin, cytokeratin (CK), type 2 3ß-hydroxysteroid dehydrogenase (3ßHSD), cytochrome P45017α, p53, p21, p27, cyclin D1, Ki-67, insulin growth facter-2 (IGF-2), and ß-catenin were undertaken for 13 tumors and 3 adjacent normal tissues. TP53 mutations in exon 2-11 were analyzed for 6 tumors and 3 blood samples.Virilization was the most common presentation (8/13, 61.5%). Immunohistochemically, p53 was positive in 8 of 13 ACTs and none in controls while p21 was positive in 12 of 13 ACTs and none in controls (P = .0036). Ki-67 was positive in 10 of 13 ACTs, but not in normal tissues (P = .0089). Although the expression of p27, cyclin D1, IGF-2 and ß-catenin were similar between the ACTs and controls, ß-catenin was noted in nuclear of 3 ACTs but not in controls. The difference of type 2 3ßHSD and P450c17α was not significant (P > .05, respectively). Four variants of TP53 were identified in the 6 tumors. C215G variant was found in 5 of 6 while A701G and G743A variants were found in 1 case, respectively. A novel C680G variant was also noted in 1 case. It was notable that C215G variant was found in the blood mononuclear cell of 3 patients.In conclusion, p53 variant and p21 overexpression, and abnormal ß-catenin distribution may be involved in the etiology and mechanism of childhood ACTs.


Assuntos
Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Virilismo/epidemiologia , 3-Hidroxiesteroide Desidrogenases/biossíntese , Neoplasias do Córtex Suprarrenal/cirurgia , Fatores Etários , Criança , Pré-Escolar , Cromogranina A/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Lactente , Fator de Crescimento Insulin-Like II/biossíntese , Queratinas/biossíntese , Antígeno Ki-67/biossíntese , Masculino , Proteínas de Ligação a Poli-ADP-Ribose/biossíntese , Fatores Sexuais , Sinaptofisina/biossíntese , Vimentina/biossíntese
17.
Monaldi Arch Chest Dis ; 89(3)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31631642

RESUMO

Multiple pulmonary nodules on chest X-ray, known commonly as cannon ball secondaries, are the classical presentation of hematogenous dissemination of a malignant tumor to the lungs. This almost always indicates an advanced stage of the disease with a very grim outlook in terms of cure or survival. In this case report, we present a patient with very extensive cannon ball lung metastases due to adrenocortical carcinoma with a more favorable prognosis. This is the first case described in the literature of cannonball lung metastases from adrenocortical tumor in a man.


Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Carcinoma Adrenocortical/complicações , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/secundário , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Idoso , Evolução Fatal , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Nódulos Pulmonares Múltiplos/patologia , Metástase Neoplásica , Remissão Espontânea , Insuficiência Respiratória/complicações , Tomografia Computadorizada por Raios X
18.
World J Surg Oncol ; 17(1): 156, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484583

RESUMO

BACKGROUND: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. MATERIAL AND METHODS: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. RESULTS: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. CONCLUSION: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Adrenocortical/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Hepatectomia/mortalidade , Laparoscopia/mortalidade , Neoplasias Hepáticas/mortalidade , Melanoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Assistência Perioperatória , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de Sobrevida
19.
Front Horm Res ; 53: 92-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31499503

RESUMO

Androgen-secreting tumors are a rare cause of hyperandrogenism of adrenal origin. Although these tumors are identified in less than 2% of patients, the prevalence of adrenocortical carcinomas is relevant (2/3 of the cases). Those tumors are associated with simultaneous elevation of several androgens, mainly androstenedione, DHEAS, and testosterone, in more than half of the patients, as measured either by immunoassay or mass spectrometry. Despite the recent advances on the pathogenesis of adrenocortical tumors, to date no driver molecular event have been identified in those tumors. This chapter provides a comprehensive review of all studies published in the last 20 years on androgen-secreting tumors, with focus on epidemiology, clinical presentation, and hormonal profile.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Androgênios/metabolismo , Hiperandrogenismo/metabolismo , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/fisiopatologia , Humanos
20.
Surgery ; 166(4): 524-533, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31472975

RESUMO

BACKGROUND: Adrenal cortical carcinoma is an aggressive malignancy and typically heralds a poor prognosis. The oncocytic subtype of this neoplasm is rare but may be associated with more favorable outcomes. METHODS: The Provincial Cancer Registry was searched for cases of adrenal cortical carcinoma between 1992 and 2017. Comprehensive chart reviews were performed and data gathered related to presentation, treatment, and outcomes. RESULTS: In the study, 82 patients with adrenal cortical carcinoma were identified. Complete data were available for 67 patients (82%). In the 41 patients who underwent resection, 9 (22%) had oncocytic subtypes. When compared with the total group of adrenal cortical carcinomas, the oncocytic subtypes were larger at presentation (19.8 cm vs 11.0 cm), more commonly symptomatic and hormonally active, and despite larger tumor size, were often early stage I and II. Recurrent disease was observed in 3 out of 9 oncocytic subtype (vs 23 out of 32 adrenal cortical carcinoma), with greater median time to recurrence (17.5 vs 8 months). Univariate analysis suggested that age, T-stage, M-stage, and overall stage were associated with survival. There was a trend toward improved overall survival for patients with oncocytic subtype on Kaplan-Meier and multivariate analysis. CONCLUSION: Despite our small numbers of patients with oncocytic subtype, our data suggest that oncocytic subtype are typically larger at presentation but more often early stage and recur less frequently than adrenocortical carcinomas. Modifications to treatment and surveillance strategies may be appropriate in this subtype.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Recidiva Local de Neoplasia/patologia , Sistema de Registros , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/mortalidade , Adulto , Alberta , Análise de Variância , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Doenças Raras , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
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