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1.
J Surg Oncol ; 129(4): 691-699, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38037311

RESUMEN

BACKGROUND: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection. METHODS: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set. RESULTS: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification. CONCLUSIONS: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Laparoscopía , Humanos , Carcinoma Corticosuprarrenal/cirugía , Carcinoma Corticosuprarrenal/patología , Nomogramas , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Neoplasias de la Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/patología , Estudios Retrospectivos
2.
Curr Treat Options Oncol ; 25(8): 1063-1072, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39066856

RESUMEN

OPINION STATEMENT: Adrenocortical cancer (ACC) is a rare and aggressive disease. Surgery has traditionally been the primary treatment for locally advanced disease with ongoing controversy around the optimal neoadjuvant and adjuvant treatment options. Unfortunately, local recurrence and the eventual development of metastatic disease is common and five-year survival rates are poor. While many trials have evaluated novel systemic agents to treat advanced adrenocortical cancer, only a few drugs have demonstrated any response at all. To date, only one drug, mitotane, is approved in the US for ACC and no regimen has clearly shown an increase in overall survival. In advanced metastatic or unresectable disease, data supports the first line regimen of EDP chemotherapy + mitotane as the primary treatment modality. In the second line, while data is limited, we would recommend consideration of immunotherapy using a PD(L)1 agent combined with a TKI/VEGF inhibitor or combination immunotherapy with PD1/CTLA-4 drugs. In all cases, we always prefer a clinical trial as available. This article reviews data from multiple studies evaluating novel systemic agents against ACC and discusses current systemic therapy combinations and ongoing clinical trials.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Protocolos de Quimioterapia Combinada Antineoplásica , Manejo de la Enfermedad , Estadificación de Neoplasias , Humanos , Carcinoma Corticosuprarrenal/terapia , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/mortalidad , Carcinoma Corticosuprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/terapia , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Terapia Molecular Dirigida , Resultado del Tratamiento , Ensayos Clínicos como Asunto
3.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39273446

RESUMEN

Genitourinary (GU) malignancies, including prostate, urothelial, kidney, testicular, penile, and adrenocortical cancers, comprise a significant burden of cancers worldwide. While many practice-changing advances have been made in the management of GU malignancies in the last decade, there is still significant room for improvement. MicroRNAs (miRNAs) are noncoding RNAs that regulate post-transcription gene expression and which have been implicated in multiple mechanisms of carcinogenesis. Therefore, they have the potential to revolutionize personalized cancer therapy, with several ongoing preclinical and clinical studies underway to investigate their efficacy. In this review, we describe the current landscape of miRNAs as diagnostics, therapeutics, and biomarkers of response for GU malignancies, reflecting a novel frontier in cancer treatment.


Asunto(s)
Biomarcadores de Tumor , MicroARNs , Neoplasias Urogenitales , Humanos , MicroARNs/genética , Neoplasias Urogenitales/genética , Neoplasias Urogenitales/terapia , Neoplasias Urogenitales/diagnóstico , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Animales
4.
Int J Mol Sci ; 25(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38791437

RESUMEN

Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.


Asunto(s)
Conexinas , Uniones Comunicantes , Humanos , Conexinas/metabolismo , Uniones Comunicantes/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Carcinogénesis/metabolismo , Carcinogénesis/patología , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Animales , Regulación Neoplásica de la Expresión Génica
5.
Rev Endocr Metab Disord ; 24(1): 85-96, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36414840

RESUMEN

Although adrenocortical carcinoma (ACC) during pregnancy is rare, a retrospective review of a case series at our hospital revealed that almost one third of our patients were women in childbearing age. Given that the age of maternity is increasing, dealing with a tumor diagnosis during pregnancy and the need for fertility planning in cancer survivors is likely to become more frequent.We thus carried out a case-based discussion regarding: i) diagnosing and treating an ACC during pregnancy; ii) patients conceiving while on mitotane; iii) ACC survivors with a maternal desire.In each of these cases, it is important to provide patients with sufficient information, to offer medical advice and psychological support, to personalize treatments in accordance with the wishes of the patient and her relatives, and to collaborate with other specialists since a multidisciplinary expert team is required to manage each case individually.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Femenino , Embarazo , Masculino , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/terapia , Carcinoma Corticosuprarrenal/patología , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/terapia , Neoplasias de la Corteza Suprarrenal/patología , Mitotano , Estudios Retrospectivos
6.
BMC Endocr Disord ; 23(1): 4, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36604647

RESUMEN

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma. CASE DESCRIPTION: Patient 1 - A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2 - A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3 - A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma. We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases. Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma. CONCLUSION: Sporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Melanoma , Anciano , Humanos , Masculino , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/genética , Carcinoma Corticosuprarrenal/cirugía , Melanoma/diagnóstico , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas B-raf , Adulto , Melanoma Cutáneo Maligno
7.
J Endocrinol Invest ; 46(3): 559-565, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36269558

RESUMEN

PURPOSE: Congenital adrenal hyperplasia (CAH) has been associated with adrenal tumors (ATs) but the relationship is still unclear. The aim was to investigate if CAH was more common in patients with adrenal tumors and their characteristics. METHODS: Using national registers all patients with an AT diagnosis (cases) and selected matched controls without AT diagnosis were included from 1st January 2005 to 31st December 2019. The patients with a CAH diagnosis were scrutinized in detail. RESULTS: ATs were diagnosed in 26,573 individuals and in none of 144,124 controls. In 20 patients with ATs and 1 control, a CAH diagnosis was present. The odds for having CAH in patients with ATs was 109 (95% CI 15-809; P < 0.0001). Among cases, 5 had a CAH diagnosis before the discovery of ATs and 15 afterwards. Half were females and two had been screened for CAH neonatally. The mean age when the ATs was discovered was 55.6 years. Adrenalectomy was performed in seven patients. Five patients had unilateral adrenalectomy before the CAH diagnosis and did not have any glucocorticoid protection. After the CAH diagnosis, 15 were initiated on glucocorticoids and 6 on mineralocorticoids. The majority diagnosed with CAH before index date had classic CAH. In individual diagnosed after index date, only three had classic CAH. The rest had nonclassical CAH. During the follow-up time of 9 years, six deceased, two of them in an adrenal crisis. CONCLUSIONS: The prevalence of CAH was greater in patients with ATs than in patients without. In all patients with ATs, CAH should be considered.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Hiperplasia Suprarrenal Congénita , Femenino , Humanos , Persona de Mediana Edad , Masculino , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperplasia Suprarrenal Congénita/diagnóstico , Estudios de Casos y Controles , Glucocorticoides , Adrenalectomía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/epidemiología
8.
Arkh Patol ; 85(4): 32-38, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37530188

RESUMEN

In 2022, the 5th edition of the of the WHO Classification of Tumours of Endocrine Organs was published, which outlines the current understanding of adrenocortical cancer (ACC), resulting from interdisciplinary research over the past decade. This article highlights the new provisions of the WHO classification for the morphological diagnosis of ACC.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/genética , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/patología
9.
Clin Endocrinol (Oxf) ; 97(4): 460-472, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34750847

RESUMEN

Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/genética , Carcinoma Corticosuprarrenal/genética , Humanos , Pronóstico , Resultado del Tratamiento
10.
Endocr Res ; 47(1): 8-17, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34340645

RESUMEN

AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm2/m2 for males and <38.5cm2/m2 for females. RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Sarcopenia , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Pronóstico , Estudios Retrospectivos , Sarcopenia/epidemiología , Sarcopenia/patología
11.
J Cell Mol Med ; 25(8): 3856-3869, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33650791

RESUMEN

Adrenocortical cancer (ACC) is a rare tumour with unfavourable prognosis, lacking an effective treatment. This tumour is characterized by IGF-II (insulin-like growth factor II) overproduction, aromatase and ERα (oestrogen receptor alpha) up-regulation. Previous reports suggest that ERα expression can be regulated by sirt1 (sirtuin 1), a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases that modulates activity of several substrates involved in cellular stress, metabolism, proliferation, senescence, protein degradation and apoptosis. Nevertheless, sirt1 can act as a tumour suppressor or oncogenic protein. In this study, we found that in H295R and SW13 cell lines, sirt1 expression is inhibited by sirtinol, a potent inhibitor of sirt1 activity. In addition, sirtinol is able to decrease ACC cell proliferation, colony and spheroids formation and to activate the intrinsic apoptotic mechanism. Particularly, we observed that sirtinol interferes with E2/ERα and IGF1R (insulin growth factor 1 receptor) pathways by decreasing receptors expression. Sirt1 involvement was confirmed by using a specific sirt1 siRNA. More importantly, we observed that sirtinol can synergize with mitotane, a selective adrenolitic drug, in inhibiting adrenocortical cancer cell growth. Collectively, our data reveal an oncogenic role for sirt1 in ACC and its targeting could implement treatment options for this type of cancer.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/patología , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , ARN Interferente Pequeño/genética , Sirtuina 1/metabolismo , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/metabolismo , Apoptosis , Humanos , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genética , Células Tumorales Cultivadas
12.
Am J Med Genet A ; 185(4): 1282-1287, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33615670

RESUMEN

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that originates in the outer layer of the adrenal gland. Most ACCs are sporadic, but a small percentage of cases are due to hereditary cancer syndromes such as Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), and familial adenomatous polyposis (FAP). Multiple endocrine neoplasia type 2A (MEN2A) is an inherited disorder that predisposes to medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia. We present here a case of ACC with both LS and MEN2A; the family and medical history were consistent with Lynch. This is, to our knowledge, the first report of a patient with ACC associated with germline mutations in RET and MSH2, and no phenotypical characteristics of MEN2A.


Asunto(s)
Carcinoma Corticosuprarrenal/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasia Endocrina Múltiple Tipo 2a/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Proto-Oncogénicas c-ret/genética , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/complicaciones , Neoplasia Endocrina Múltiple Tipo 2a/patología , Linaje
13.
Expert Opin Emerg Drugs ; 26(2): 165-178, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33896321

RESUMEN

Introduction: Adrenocortical cancer (ACC) is a rare and aggressive disease with a median survival of 14-17 months and 5-year survival of around 20% for advanced disease. Emerging evidence of sub-groups of ACC with specific molecular drivers indicate ACC may be amenable to inhibition of receptor tyrosine kinases involved in growth and angiogenic signaling. A significant subset of patients may also be responsive to immune strategies.Areas covered: This review outlines approaches of targeting upregulated growth pathways including Insulin-like Growth Factor, Vascular Endothelial Growth Factor, Fibroblast Growth Factor and Epidermal Growth Factor Receptor in ACC. Data of immune checkpoint blockade with nivolumab, ipilimumab, pembrolizumab and avelumab is explored in detail. Genomic studies indicate that up to 40% of ACC are driven by dysregulated WNT and glucocorticoid signaling, special focus is placed on emerging drugs in these pathways.Expert opinion: Progress in the treatment of ACC has faced challenges stemming from the rarity of the disease. Given recent advances in the understanding of the molecular pathogenesis of ACC, a window of opportunity has now opened to make significant progress in developing therapeutic options that target key pathways such as excessive glucocorticoid signaling, WNT signaling, cell cycle and immune checkpoints.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Antineoplásicos Inmunológicos/farmacología , Neoplasias de la Corteza Suprarrenal/inmunología , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/inmunología , Carcinoma Corticosuprarrenal/patología , Animales , Diseño de Fármacos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Tasa de Supervivencia
14.
Arkh Patol ; 83(3): 10-18, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-33822549

RESUMEN

Adrenocortical cancer (ACC) is a rare endocrine malignancy of the adrenal cortex, which has an unfavorable prognosis and extremely aggressive clinical behavior in most cases. Nevertheless, cases of a more favorable disease course with late metastasis and slow progression have been described. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in the 4th edition of the Classification of Tumors of the Endocrine Organs identified histological variants of ACC, such as classical, oncocytic, myxoid, and sarcomatoid ones, indicating the morphological heterogeneity of this tumor. OBJECTIVE: To provide a detailed description of the morphological variants of ACC with an emphasis on their histological characteristics and the expression of immunohistochemical markers. MATERIALS AND METHODS: A total of 75 cases of ACC were analyzed in the adult population diagnosed as having the morphological variants in accordance with the International Histological Classification of Adrenal Tumors (WHO, 2017). Monoclonal antibodies to SF1, Inhibin A, Melan A, Ki-67, p53, and antimitochondrial antibodies were used for immunohistochemical diagnosis. RESULTS: The classic, oncocytic, and myxoid subtypes of ACC were found in 51 (68%), 15 (20%), and 9 (12%) cases, respectively. The functional activity of the tumors was observed in 43% (n=18) in the classic variant of ACC; moreover, the clinical picture was manifested by the symptoms of hypercorticism (38%) and virilization (5%). There were no significant differences in hormonal activity between different morphological variants. The characteristics of the above histological variants of the tumor was determined with a description of growth patterns that can improve the diagnosis of ACC. The diagnosis of ACC can be confirmed by an immunohistochemical study; the required minimum panel of markers should include SF1, Melan A, and Inhibin A. The Ki-67 proliferative activity index showed significant differences (p=0.0056) when it was determined in the morphological variants of ACC. CONCLUSION: Despite the determination of a minimal immunohistochemical panel to confirm the diagnosis of ACC, it is important to remember that each histological variant may be characterized by the different expression of immunohistochemical markers. The identification of morphological variants of ACC and the use of specific, sensitive, and prognostically significant immunohistochemical markers will allow clinicians and pathologists to more accurately judge the biological properties of this tumor and the clinical course of the disease.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Neoplasias de las Glándulas Suprarrenales , Carcinoma Corticosuprarrenal , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/genética , Adulto , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Humanos , Pronóstico
15.
J Endocrinol Invest ; 43(3): 357-367, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31587178

RESUMEN

PURPOSE: Mitotane is the only chemotherapeutic agent available for the treatment of adrenocortical carcinoma (ACC), however, the anti-neoplastic efficacy is limited due to several side-effects in vivo. There is, therefore, a need of exploring for new anti-tumoral agents which can be used either alone or in combination with mitotane. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) acts as an anti-proliferative agent in human cancer by inhibiting the Wnt/beta-catenin pathway through the vitamin D receptor (VDR). The aim of this study was to study the effects of mitotane and 1α,25(OH)2D3, individually or in combination, in an in vitro model with H295R ACC cells, and to elucidate the molecular events behind their effects involving the Wnt/beta-catenin signaling. METHODS AND RESULTS: Multiple concentrations of mitotane and 1α,25(OH)2D3, individually or in combination, were tested on H295R cells for 24-96 h, and the effects analysed by MTT. A reduction in cell growth was observed in a dose/time-dependent manner for both mitotane and 1α,25(OH)2D3. In addition, a combination of clinically sub-therapeutic concentrations of mitotane with 1α,25(OH)2D3, had an additive anti-proliferative effect (Combination Index = 1.02). In a wound healing assay, individual treatments of both mitotane and 1α,25(OH)2D3 reduced the migration ability of H295R cells, with the effect further enhanced on combining both the agents. Western blotting and qRT-PCR analysis showed a modulation of the Wnt/beta-catenin and VDR signaling pathways. CONCLUSION: Our results show an additive effect of mitotane and 1α,25(OH)2D3 on the inhibition of H295R ACC cell growth and viability, and suggest that molecular mechanisms of their effects involve a functional link between VDR and Wnt/beta-catenin pathways.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/efectos de los fármacos , Carcinoma Corticosuprarrenal/metabolismo , Calcitriol/farmacología , Mitotano/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Línea Celular Tumoral , Humanos , beta Catenina/metabolismo
16.
Pol Merkur Lekarski ; 48(288): 443-445, 2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33387434

RESUMEN

Primary cardiac tumors are extremely uncommon but metastases can result from direct invasion from the mediastinum, hematogenous spread or extension of the tumor into the vena cava and the right atrium. A CASE REPORT: A 37-year-old male with no previous history of chronic diseases was admitted to the hospital due to non-specific chest discomfort, non-productive cough and weakness lasting for several weeks. Physical examination was unremarkable except for tachycardia and bibasal rales. Chest radiogram revealed multiple pulmonary lesions suggesting metastases. A mass in the right adrenal gland was found on abdominal ultrasound and CT scan. In addition, a pathological lesion in the inferior vena cava extending to the right atrium was detected. Echocardiography revealed a pedunculated mass measuring 2.3x1.5 cm, located in the right atrium, which originated from the inferior vena cava. During the diastole, it prolapsed to the right ventricle but did not significantly affect blood flow through the tricuspid valve. Adrenal tumor biopsy revealed adrenocortical cancer and treatment with mitotane was started. After a seizure episode, brain MRI was performed and showed metastases surrounded by edema. Due to the patient's poor general condition and progression of the disease during mitotane treatment was later withdrawn and the patient was referred for the hospice care where he died 2 months later. CONCLUSIONS: Adrenocortical cancer is a rare malignant neoplasm with an estimated annual incidence of 4-12 cases per 1,000,000. It is characterized by a tendency for local invasion and multiple metastases to the lungs, liver and bones. In the literature, there are only a few cases of adrenocortical cancer directly extending from the inferior vena cava to the right atrium.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias Cardíacas , Adulto , Atrios Cardíacos/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico por imagen , Humanos , Masculino , Vena Cava Inferior/diagnóstico por imagen
17.
J Surg Oncol ; 120(8): 1450-1455, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31733070

RESUMEN

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.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/mortalidad , Carcinoma Corticosuprarrenal/mortalidad , Recuento de Linfocitos , Monocitos/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/cirugía , Adulto , Biomarcadores/sangre , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Factores de Tiempo
18.
Int J Cancer ; 143(4): 944-957, 2018 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-29516499

RESUMEN

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC. We identified N-myc downstream-regulated gene family members 2 and 4 (NDRG2 and NDRG4) as targets of miR-483-5p and miR-139-5p, respectively. NDRG2 and NDRG4 expressions were inversely correlated respectively with miR-483-5p and miR-139-5p levels in aggressive ACC samples from two independent cohorts of 20 and 44 ACC. Moreover, upregulation of miR-139-5p and downregulation of NDRG4 demonstrated a striking prognostic value. A direct interaction between miR-483-5p or miR-139-5p and their targets was demonstrated in reporter assays. Downregulation of miR-483-5p or miR-139-5p in the ACC cell lines NCI-H295R and SW13 increased NDRG2 or NDRG4 mRNA and protein expression, compromised adrenocortical cancer cell invasiveness and anchorage-independent growth. MiR-483-5p or miR-139-5p overexpression and NDRG2 or NDRG4 inhibition produce similar changes, which are rescued by NDRG2 or NDRG4 ectopic expression. We established that key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. Collectively, our data show for the first time that miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes promote ACC aggressiveness, with potential implications for prognosis and therapeutic interventions in adrenocortical malignancies.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/patología , Regulación Neoplásica de la Expresión Génica , Genes myc , MicroARNs/fisiología , Familia de Multigenes , Regiones no Traducidas 3' , Apoptosis/fisiología , Adhesión Celular/fisiología , Ciclo Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Células HEK293 , Humanos , MicroARNs/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Estadificación de Neoplasias , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Pronóstico , ARN Mensajero/genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba
19.
Acta Chir Belg ; 118(2): 113-119, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28385115

RESUMEN

BACKGROUND: Transcatheter arterial embolization (TAE) is an effective minimally invasive adjunct to surgery for the management and/or palliation of adrenal tumors. METHODS: In this case study, we reported three patients who underwent preoperative TAE before adrenalectomy for large hypervascular adrenal tumors. All patients underwent preoperative embolization 24 h before the operation and were then followed up at the intensive care unit surgery. RESULTS: The largest diameter of the adrenal lesions ranged between 8 and 17 cm. Hypertensive attack occurred in one patient with pheochromocytoma during embolization. No other complications associated with the procedure was noted. The adrenal tumors were totally excised in all patients. The major intraoperative findings associated with preoperative embolization were marked reduction in hypervascularity and the decrease in the size of collateral vessels. No major hemorrhage necessitating blood transfusion were noted during surgery. CONCLUSIONS: Preoperative embolization of large hypervascular adrenal masses could reduce perioperative blood loss by reducing tumor vascularity.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Arterias , Embolización Terapéutica/métodos , Feocromocitoma/cirugía , Cuidados Preoperatorios/métodos , Neoplasias de las Glándulas Suprarrenales/irrigación sanguínea , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Adulto , Angiografía de Substracción Digital , Femenino , Humanos , Feocromocitoma/irrigación sanguínea , Feocromocitoma/diagnóstico , Adulto Joven
20.
Orv Hetil ; 159(7): 245-251, 2018 Feb.
Artículo en Húngaro | MEDLINE | ID: mdl-29429354

RESUMEN

Adrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression. Their altered expression has been described in many tumours. Several tissue microRNAs, such as miR-483-5p, miR-503, miR-210, miR-335 and miR-195 were found to be differentially expressed among benign and malignant adrenocortical tumours, and these could also have pathogenic relevance. Due to their tissue specific and stable expression, microRNAs can be exploited in diagnostics as well. As the histological diagnosis of adrenocortical malignancy is difficult, microRNAs might be of help in the establishment of malignancy. Novel data show that microRNAs are secreted in various body fluids, projecting their applicability as biomarkers as part of liquid biopsy. In this review, we attempt to present a synopsis on the pathogenic relevance of microRNAs in adrenocortical tumours and their potential diagnostic applicability. Orv Hetil. 2018; 159(7): 245-251.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , Adenoma Corticosuprarrenal/genética , Carcinoma Corticosuprarrenal/genética , Humanos
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