Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
Adrenocortical Carcinoma
share announcement

Adrenocortical Carcinoma

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 67619

Special Issue Editors

Prof. Dr. Alfredo Berruti

E-Mail Website
Guest Editor
Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Brescia, Italy
Interests: adrenal cortex carcinoma; mitotane; gastroenteropancreatic neuroendocrine tumor; cancer; carcinoid tumor; kidney metastasis; pazopanib; cabozantinib; adrenocortical carcinoma; breast cancer; chemotherapy; 18F-FDG PET/CT
Prof. Sandra Sigala

E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, Section of Pharmacology, University of Brescia, Brescia, Italy
Interests: Pharmacology; Preclinical and translational research; Oncology
Prof. Guido Alberto Massimo Tiberio

E-Mail Website
Guest Editor
Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
Interests: adrenal diseases; gastroenteric surgical oncology; peritoneal surface malignancies; hepatic malignancies; pancreatic diseases; retroperitoneal sarcoma; laparoscopic surgery; translational research

Special Issue Information

Dear Colleagues,

Adrenocortical carcinoma (ACC) is a rare endocrine malignant disease. The management of ACC patients is challenging. Surgery is the mainstay of therapy and represents the only treatment modality that can offer patients a chance of cure. Systemic therapy is still based on mitotane, or the association of mitotane with etoposide, doxorubicin, and cisplatin (EDP-M scheme). The molecular target therapies and immunotherapies tested so far have substantially failed to demonstrate a significant efficacy in ACC.

New therapies are needed, but the rarity of the disease hampers the performance of prospective clinical trials. Since only a few studies can be carried out in this rare pathology, the accurate identification of strong biological rationales deriving from sound preclinical studies is crucial before designing a new trial.

At the same time, we need to optimize the available strategies by the introduction of neoadjuvant and adjuvant therapies before and after surgery in patients with early ACC and the integration of systemic therapies and surgery in advanced ACC.

The prognosis of ACC patients is often dismal but heterogeneous, and the availability of robust prognostic and predictive parameters is of paramount importance.

This Special Issue will focus on the current state of the art and future prospects in the management of ACC at both clinical and preclinical level.

Prof. Alfredo Berruti
Prof. Sandra Sigala
Prof. Guido Alberto Massimo Tiberio
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adrenocortical carcinoma
  • surgery
  • chemotherapy
  • mitotane
  • prognostic factors
  • molecular biology
  • target therapies
  • immunotherapy
  • in vitro studies
  • in vivo studies
  • HIPEC (hyperthermic intraperitoneal peroperative chemotherapy)
  • recurrent disesase

Published Papers (23 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 204 KiB  
Editorial
Adrenocortical Carcinoma
by Alfredo Berruti, Guido Alberto Massimo Tiberio and Sandra Sigala
Cancers 2021, 13(5), 1077; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13051077 - 03 Mar 2021
Cited by 3 | Viewed by 1476
Abstract
Adrenocortical carcinoma (ACC) is an extremely rare disease, the incidence of which is 0 [...] Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)

Research

Jump to: Editorial, Review

13 pages, 1502 KiB  
Article
Prognostic and Monitoring Value of Circulating Tumor Cells in Adrenocortical Carcinoma: A Preliminary Monocentric Study
by Giulia Cantini, Letizia Canu, Roberta Armignacco, Francesca Salvianti, Giuseppina De Filpo, Tonino Ercolino, Gabriella Nesi, Mario Maggi, Massimo Mannelli, Pamela Pinzani and Michaela Luconi
Cancers 2020, 12(11), 3176; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113176 - 29 Oct 2020
Cited by 11 | Viewed by 1940
Abstract
Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents [...] Read more.
Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents a source of tumor material within a minimally invasive blood draw that allows the recovery of circulating tumor cells (CTCs). CTCs have been recently shown to be detectable in ACC. In the present paper, we evaluated the prognostic value of CTCs obtained by size-filtration in a small pilot cohort of 19 ACC patients. We found CTCs in 68% of pre-surgery and in 38% of post-surgery blood samples. In addition, CTC clusters (CTMs) and cancer associated macrophages (CAMLs) were detectable in some ACC patients. The median number of CTCs significantly decreased after the mass removal. Finally, stratifying patients in high and low pre-surgery CTC number groups, assuming the 75th percentile CTC value as cut-off, CTCs significantly predicted patients’ overall survival (log rank = 0.005), also in a multivariate analysis adjusted for age and tumor stage. In conclusion, though preliminary and performed in a small cohort of patients, our study suggests that CTC number may represent a promising marker for prognosis and disease monitoring in ACC. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Graphical abstract

15 pages, 994 KiB  
Article
Development and Internal Validation of a Multivariable Prediction Model for Adrenocortical-Carcinoma-Specific Mortality
by Madeleine H. T. Ettaieb, Sander M. J. van Kuijk, Annelies de Wit-Pastoors, Richard A. Feelders, Eleonora P. M. Corssmit, Elisabeth M. W. Eekhoff, Paul van der Valk, Henri J. L. M. Timmers, Michiel N. Kerstens, Heinz-Josef Klümpen, Rachel S. van Leeuwaarde, Bas Havekes and Harm R. Haak
Cancers 2020, 12(9), 2720; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092720 - 22 Sep 2020
Cited by 6 | Viewed by 2088
Abstract
Adrenocortical carcinoma (ACC) has an incidence of about 1.0 per million per year. In general, survival of patients with ACC is limited. Predicting survival outcome at time of diagnosis is a clinical challenge. The aim of this study was to develop and internally [...] Read more.
Adrenocortical carcinoma (ACC) has an incidence of about 1.0 per million per year. In general, survival of patients with ACC is limited. Predicting survival outcome at time of diagnosis is a clinical challenge. The aim of this study was to develop and internally validate a clinical prediction model for ACC-specific mortality. Data for this retrospective cohort study were obtained from the nine centers of the Dutch Adrenal Network (DAN). Patients who presented with ACC between 1 January 2004 and 31 October 2013 were included. We used multivariable Cox proportional hazards regression to compute the coefficients for the prediction model. Backward stepwise elimination was performed to derive a more parsimonious model. The performance of the initial prediction model was quantified by measures of model fit, discriminative ability, and calibration. We undertook an internal validation step to counteract the possible overfitting of our model. A total of 160 patients were included in the cohort. The median survival time was 35 months, and interquartile range (IQR) 50.7 months. The multivariable modeling yielded a prediction model that included age, modified European Network for the Study of Adrenal Tumors (mENSAT) stage, and radical resection. The c-statistic was 0.77 (95% Confidence Interval: 0.72, 0.81), indicating good predictive performance. We developed a clinical prediction model for ACC-specific mortality. ACC mortality can be estimated using a relatively simple clinical prediction model with good discriminative ability and calibration. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

14 pages, 4731 KiB  
Article
Adrenocortical Carcinoma and CT Assessment of Therapy Response: The Value of Combining Multiple Criteria
by Roberta Ambrosini, Maria Carolina Balli, Marta Laganà, Martina Bertuletti, Luca Bottoni, Filippo Vaccher, Deborah Cosentini, Marco Di Terlizzi, Sandra Sigala, Salvatore Grisanti, Guido Alberto Massimo Tiberio, Alfredo Berruti and Luigi Grazioli
Cancers 2020, 12(6), 1395; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061395 - 28 May 2020
Cited by 7 | Viewed by 2262
Abstract
We evaluated tumor response at Computed Tomography (CT) according to three radiologic criteria: RECIST 1.1, CHOI and tumor volume in 34 patients with metastatic adrenocortical carcinoma (ACC) submitted to standard chemotherapy. These three criteria agreed in defining partial response, stable or progressive disease [...] Read more.
We evaluated tumor response at Computed Tomography (CT) according to three radiologic criteria: RECIST 1.1, CHOI and tumor volume in 34 patients with metastatic adrenocortical carcinoma (ACC) submitted to standard chemotherapy. These three criteria agreed in defining partial response, stable or progressive disease in 24 patients (70.5%). Partial response (PR) was observed in 29.4%, 29.4% and 41.2% of patients according to RECIST 1.1, CHOI and tumor volume, respectively. It was associated with a favorable prognosis, regardless of the criterion adopted. The concordance of all the 3 criteria in defining the disease response identified 8 patients (23.5%) which displayed a very good prognosis: median progression free survival (PFS) and overall survival (OS) 14.9 and 37.7 months, respectively. Seven patients (20.6%) with PR assessed by one or two criteria, however, still had a better prognosis than non-responding patients, both in terms of PFS: median 12.3 versus 9.9 months and OS: 21 versus 12.2, respectively. In conclusions, the CT assessment of disease response of ACC patients to chemotherapy with 3 different criteria is feasible and allows the identification of a patient subset with a more favorable outcome. PR with at least one criterion can be useful to early identify patients that deserve continuing the therapy. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

13 pages, 1343 KiB  
Article
Hyperthermic Intraperitoneal Chemotherapy for Primary or Recurrent Adrenocortical Carcinoma. A Single Center Study
by Guido Alberto Massimo Tiberio, Vittorio Ferrari, Zeno Ballarini, Giovanni Casole, Marta Laganà, Michele Gritti, Elisa Arici, Salvatore Grisanti, Riccardo Nascimbeni, Sandra Sigala, Alfredo Berruti and Arianna Coniglio
Cancers 2020, 12(4), 969; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12040969 - 14 Apr 2020
Cited by 3 | Viewed by 1878
Abstract
Background. This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances. Methods. Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC [...] Read more.
Background. This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances. Methods. Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC for primary (SP, 13 patients) or recurrent (SR, 14 patients, 17 treatments) ACC. Safety was evaluated by means of procedural morbidity and mortality. Survival performances included multiple end points: local/peritoneal disease-free survival (l/pDFS), overall progression-free survival (OPFS), and overall survival (OS). Results. In the SP group, mortality was nil and morbidity was 46% (major 23%). At a median follow-up of 25 months, the median value for all the different survival measures had not been reached. Mortality was also nil in the SR group. However, morbidity was 77% (major 18%). Median l/pDFS and OPFS were 12 ± 4 and 8 ± 2 months, respectively. At a median follow-up of 30 months, median OS had not been reached. Conclusion. Surgery and HIPEC is an invasive procedure. Its employment in the surgery for primary setting deserves attention as it may affect oncologic outcomes positively. Its value in the management of recurrences seems less appreciable, albeit it may find its place in the multimodal management of a rare disease for which multiple therapeutic options do not yet exist. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

12 pages, 2724 KiB  
Article
Efficacy of the EDP-M Scheme Plus Adjunctive Surgery in the Management of Patients with Advanced Adrenocortical Carcinoma: The Brescia Experience
by Marta Laganà, Salvatore Grisanti, Deborah Cosentini, Vittorio Domenico Ferrari, Barbara Lazzari, Roberta Ambrosini, Chiara Sardini, Alberto Dalla Volta, Carlotta Palumbo, Pietro Luigi Poliani, Massimo Terzolo, Sandra Sigala, Guido Alberto Massimo Tiberio and Alfredo Berruti
Cancers 2020, 12(4), 941; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12040941 - 10 Apr 2020
Cited by 38 | Viewed by 3530
Abstract
Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for [...] Read more.
Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1–12.8) and 18.7 months (95% CI: 14.6–22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Graphical abstract

15 pages, 2446 KiB  
Article
Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells
by Andrea Abate, Elisa Rossini, Sara Anna Bonini, Martina Fragni, Deborah Cosentini, Guido Albero Massimo Tiberio, Diego Benetti, Constanze Hantel, Marta Laganà, Salvatore Grisanti, Massimo Terzolo, Maurizio Memo, Alfredo Berruti and Sandra Sigala
Cancers 2020, 12(4), 928; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12040928 - 09 Apr 2020
Cited by 15 | Viewed by 3009
Abstract
Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC [...] Read more.
Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /β catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

13 pages, 888 KiB  
Article
Mitotane Concentrations Influence Outcome in Patients with Advanced Adrenocortical Carcinoma
by Soraya Puglisi, Anna Calabrese, Vittoria Basile, Filippo Ceccato, Carla Scaroni, Barbara Altieri, Silvia Della Casa, Paola Loli, Rosario Pivonello, Maria Cristina De Martino, Letizia Canu, Marco Russo, Giuseppe Badalamenti, Massimo Torlontano, Antonio Stigliano, Francesco Ferraù, Giorgio Arnaldi, Laura Saba, Alessandra Quirino, Paola Perotti, Paola Berchialla and Massimo Terzoloadd Show full author list remove Hide full author list
Cancers 2020, 12(3), 740; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030740 - 20 Mar 2020
Cited by 29 | Viewed by 3358
Abstract
Mitotane is the main option of treatment for advanced adrenocortical carcinoma (ACC). However, limited evidence is available regarding the impact of plasma mitotane levels on patient outcome. To address this question, we retrospectively analyzed patients with advanced ACC treated with mitotane for ≥3 [...] Read more.
Mitotane is the main option of treatment for advanced adrenocortical carcinoma (ACC). However, limited evidence is available regarding the impact of plasma mitotane levels on patient outcome. To address this question, we retrospectively analyzed patients with advanced ACC treated with mitotane for ≥3 months, with ≥3 measurements of plasma mitotane reported in the Lysosafe Online® database (HRA Pharma, France), followed at 12 tertiary centers in Italy from 2005 to 2017. We identified 80 patients, initially treated with mitotane alone (56.2%) or plus chemotherapy (43.8%). The preference toward combination therapy was given to de novo stage IV ACC and younger patients. After the first line of treatment, 25% of valid cases experienced clinical benefit (14.5% objective response, 10.5% stabilization of disease) and 75% progression, without differences between the groups of treatment. Patients with progression had a lower time in the target range (TTR) of plasma mitotane and an unfavorable outcome. Death occurred in 76.2% of cases and multivariate analysis showed that clinical benefit after first treatment and longer TTR were favorable predictors of overall survival (OS). In conclusion, the present findings support the importance of mitotane monitoring and strengthen the concept of a therapeutic window for mitotane. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

11 pages, 1630 KiB  
Article
Early Postoperative Circulating miR-483-5p Is a Prognosis Marker for Adrenocortical Cancer
by Maurine Oreglia, Silviu Sbiera, Martin Fassnacht, Laurent Guyon, Josiane Denis, Justine Cristante, Olivier Chabre and Nadia Cherradi
Cancers 2020, 12(3), 724; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030724 - 19 Mar 2020
Cited by 17 | Viewed by 2312
Abstract
We have previously identified serum miR-483-5p as a preoperative diagnosis and prognosis biomarker for adrenocortical cancer (ACC). Here, we aimed to determine whether circulating miR-483-5p levels measured 3 months post-operatively distinguished patients with good prognosis (no recurrence for at least 3 years; NR3yrs) [...] Read more.
We have previously identified serum miR-483-5p as a preoperative diagnosis and prognosis biomarker for adrenocortical cancer (ACC). Here, we aimed to determine whether circulating miR-483-5p levels measured 3 months post-operatively distinguished patients with good prognosis (no recurrence for at least 3 years; NR3yrs) from patients with poor prognosis (recurrence or death within 3 years after surgery; R < 3yrs). We conducted a single-center retrospective analysis using sera from 48 patients with ACC that were initially non-metastatic and treated by surgery. Sera sampled within 3 months after surgery were available in 26 patients. MiR-483-5p absolute circulating levels were measured using quantitative PCR. Thirteen patients showed a recurrence before 3 years (=R < 3yrs). Thirteen patients showed no recurrence within 3 years, including 11 patients with a follow-up longer than 3 years (=NR3yrs). Serum miR-483-5p levels were higher in R < 3yrs than in NR3yrs: 1,541,990 ± 428,377 copies/mL vs. 388,457 ± 62,169 copies/mL (p = 0.002). Receiver operating characteristic analysis showed that a value of 752,898 copies/mL distinguished R < 3yrs from NR3yrs with 61.5% sensitivity (CI 31.6–86.1) and 100% specificity (CI 71.5–100) with an area under the curve of 0.853. Patients with a value below this threshold had a significantly longer recurrence-free and overall survival. In multivariate analysis, miR-483-5p provided the single best prognostic value for recurrence-free survival (RFS) (hazard ratio (HR) for recurrence 5.98, p < 0.011) but not for overall survival. Our study suggests that serum miR-483-5p is a potent early post-operative biomarker for ACC prognosis that might be a better predictor of RFS than currently used markers. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

20 pages, 2173 KiB  
Article
Cancer-testis Antigen FATE1 Expression in Adrenocortical Tumors Is Associated with A Pervasive Autoimmune Response and Is A Marker of Malignancy in Adult, but Not Children, ACC
by Mabrouka Doghman-Bouguerra, Pascal Finetti, Nelly Durand, Ivy Zortéa S. Parise, Silviu Sbiera, Giulia Cantini, Letizia Canu, Ségolène Hescot, Mirna M. O. Figueiredo, Heloisa Komechen, Iuliu Sbiera, Gabriella Nesi, Angelo Paci, Abir Al Ghuzlan, Daniel Birnbaum, Eric Baudin, Michaela Luconi, Martin Fassnacht, Bonald C. Figueiredo, François Bertucci and Enzo Lalliadd Show full author list remove Hide full author list
Cancers 2020, 12(3), 689; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030689 - 14 Mar 2020
Cited by 15 | Viewed by 2791
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

9 pages, 414 KiB  
Article
Recovery of Adrenal Insufficiency Is Frequent After Adjuvant Mitotane Therapy in Patients with Adrenocortical Carcinoma
by Jonathan Poirier, Nadia Gagnon, Massimo Terzolo, Soraya Puglisi, Nada El Ghorayeb, Anna Calabrese, André Lacroix and Isabelle Bourdeau
Cancers 2020, 12(3), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030639 - 10 Mar 2020
Cited by 17 | Viewed by 2468
Abstract
Mitotane is a steroidogenesis inhibitor and adrenolytic drug used for treatment of adrenocortical cancer (ACC). Mitotane therapy causes adrenal insufficiency requiring glucocorticoid replacement in all patients. However, it is unclear whether chronic therapy with mitotane induces complete destruction of zona fasciculata and whether [...] Read more.
Mitotane is a steroidogenesis inhibitor and adrenolytic drug used for treatment of adrenocortical cancer (ACC). Mitotane therapy causes adrenal insufficiency requiring glucocorticoid replacement in all patients. However, it is unclear whether chronic therapy with mitotane induces complete destruction of zona fasciculata and whether hypothalamic-pituitary-adrenal (HPA) axis can recover after treatment cessation. Our objective was to assess the HPA axis recovery in a cohort of patients after cessation of adjuvant mitotane therapy for ACC. We retrospectively reviewed patient files with stage I-II-III ACC in two referral centers in Canada and Italy. Data on demographics, tumor characteristics, hormonal profile, and HPA axis were collected. Data from 23 patients with pathologically proven ACC treated with adjuvant mitotane for a minimum of two years were analyzed. Eight patients were males and 15 were females and the median age was 41 years old (range 18 to 73). After mitotane cessation, 18/23 (78.3%) patients achieved a complete HPA axis recovery while 3/23 (13.0%) were unable to tolerate glucocorticoid withdrawal despite having normal hormonal test values and 2/23 (8.7%) never achieved recovery. The mean time interval between mitotane cessation and HPA axis recovery was 2.7 years. A high proportion of patients achieved HPA axis recovery following cessation of mitotane adjuvant therapy. However, complete recovery was often delayed up to 2.5 years and regular assessment of the hormonal profile is required. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

12 pages, 834 KiB  
Article
High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53
by Vania Balderrama Brondani, Luciana Montenegro, Amanda Meneses Ferreira Lacombe, Breno Marchiori Magalhães, Mirian Yumie Nishi, Mariana Ferreira de Assis Funari, Amanda de Moraes Narcizo, Lais Cavalca Cardoso, Sheila Aparecida Coelho Siqueira, Maria Claudia Nogueira Zerbini, Francisco Tibor Denes, Ana Claudia Latronico, Berenice Bilharinho Mendonca, Madson Queiroz Almeida, Antonio Marcondes Lerario, Ibere Cauduro Soares and Maria Candida Barisson Villares Fragoso
Cancers 2020, 12(3), 621; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030621 - 07 Mar 2020
Cited by 5 | Viewed by 2512
Abstract
Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to [...] Read more.
Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for the MMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of altered MMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

11 pages, 1378 KiB  
Article
Germline Variants in Phosphodiesterase Genes and Genetic Predisposition to Pediatric Adrenocortical Tumors
by Emilia Modolo Pinto, Fabio R. Faucz, Luana Z. Paza, Gang Wu, Elizabeth S. Fernandes, Jerome Bertherat, Constantine A. Stratakis, Enzo Lalli, Raul C. Ribeiro, Carlos Rodriguez-Galindo, Bonald C. Figueiredo and Gerard P. Zambetti
Cancers 2020, 12(2), 506; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12020506 - 22 Feb 2020
Cited by 17 | Viewed by 4648
Abstract
Phosphodiesterases (PDEs) form a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides adenosine 3′5′-cyclic monophosphate (cAMP) and guanosine 3′5′-cyclic monophosphate (cGMP) to their inactive 5′ monophosphates. cAMP plays a critical role as a second messenger in endocrine tissues, and activation of [...] Read more.
Phosphodiesterases (PDEs) form a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides adenosine 3′5′-cyclic monophosphate (cAMP) and guanosine 3′5′-cyclic monophosphate (cGMP) to their inactive 5′ monophosphates. cAMP plays a critical role as a second messenger in endocrine tissues, and activation of cAMP signaling has been reported in endocrine tumors. Germline variants in PDEs have been associated with benign cortisol-secreting adrenocortical adenomas and testicular germ cell cancer but not adrenocortical carcinoma. We performed whole genome sequencing (WGS) and whole exome sequencing (WES) of paired blood and tumor samples from 37 pediatric adrenocortical tumors (ACTs). Germline inactivating variants in PDEs were observed in 9 of 37 (24%) patients. Tumor DNA analysis revealed loss of heterozygosity, with maintenance of the mutated allele in all cases. Our results suggest that germline variants in PDEs and other regulators of the cAMP-signaling pathway may contribute to pediatric adrenocortical tumorigenesis, perhaps by cooperating with germline hypomorphic mutant TP53 alleles and uniparental disomy of chromosome 11p15 (Beckwith–Wiedemann syndrome). Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

17 pages, 1148 KiB  
Article
Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study
by Barbara Altieri, Silviu Sbiera, Sabine Herterich, Silvia De Francia, Silvia Della Casa, Anna Calabrese, Alfredo Pontecorvi, Marcus Quinkler, Tina Kienitz, Massimo Mannelli, Letizia Canu, Anna Angelousi, Vasileios Chortis, Matthias Kroiss, Massimo Terzolo, Martin Fassnacht and Cristina L. Ronchi
Cancers 2020, 12(2), 359; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12020359 - 04 Feb 2020
Cited by 24 | Viewed by 3121
Abstract
Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms [...] Read more.
Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2% vs 51.7%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55% of patients with CYP2B6*6 vs. 28.2% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

12 pages, 1961 KiB  
Article
Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
by Amanda Meneses Ferreira Lacombe, Iberê Cauduro Soares, Beatriz Marinho de Paula Mariani, Mirian Yumie Nishi, João Evangelista Bezerra-Neto, Helaine da Silva Charchar, Vania Balderrama Brondani, Fabio Tanno, Victor Srougi, José Luiz Chambo, Ricardo Miguel Costa de Freitas, Berenice Bilharinho Mendonca, Ana O. Hoff, Madson Q. Almeida, Isabel Weigand, Matthias Kroiss, Maria Claudia Nogueira Zerbini and Maria Candida Barisson Villares Fragoso
Cancers 2020, 12(1), 247; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12010247 - 19 Jan 2020
Cited by 20 | Viewed by 3222
Abstract
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 [...] Read more.
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score ≥ 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0–4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score ≤ 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26–3.66; p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09–4.06; p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

22 pages, 3580 KiB  
Article
The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model
by Roberta Armignacco, Giulia Cantini, Giada Poli, Daniele Guasti, Gabriella Nesi, Paolo Romagnoli, Massimo Mannelli and Michaela Luconi
Cancers 2019, 11(12), 1931; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11121931 - 04 Dec 2019
Cited by 18 | Viewed by 2873
Abstract
Metabolic interplay between the tumor microenvironment and cancer cells is a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare [...] Read more.
Metabolic interplay between the tumor microenvironment and cancer cells is a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare endocrine neoplasia with a poor prognosis, cancer cells often infiltrate the fat mass surrounding the adrenal organ, enabling possible crosstalk with the adipose cells. Here, by using an in vitro co-culture system, we show that the interaction between adipose-derived stem cells (ASCs) and the adrenocortical cancer cell line H295R leads to metabolic and functional reprogramming of both cell types: cancer cells limit differentiation and increase proliferation of ASCs, which in turn support tumor growth and invasion. This effect associates with a shift from the paracrine cancer-promoting IGF2 axis towards an ASC-associated leptin axis, along with a shift in the SDF-1 axis towards CXCR7 expression in H295R cells. In conclusion, our findings suggest that adipose precursors, as pivotal components of the ACC microenvironment, promote cancer cell reprogramming and invasion, opening new perspectives for the development of more effective therapeutic approaches. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Graphical abstract

16 pages, 1580 KiB  
Article
Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil
by Tatiana E. J. Costa, Viviane K. Q. Gerber, Humberto C. Ibañez, Viviane S. Melanda, Ivy Z. S. Parise, Flora M. Watanabe, Mara A. D. Pianovski, Carmem M. C. M. Fiori, Ana L. M. R. Fabro, Denise B. da Silva, Diancarlos P. Andrade, Heloisa Komechen, Monalisa C. Mendes, Edna Carboni, Ana Paula Kuczynski, Emanuelle N. Souza, Mariana M. Paraizo, Marilea V. C. Ibañez, Laura M. Castilho, Amanda F. Cruz, Thuila F. da Maia, Cleber Machado-Souza, Roberto Rosati, Claudia S. Oliveira, Guilherme A. Parise, Jaqueline D. C. Passos, José R. S. Barbosa, Mirna M. O. Figueiredo, Leniza Lima, Tiago Tormen, Cesar C. Sabbaga, Sylvio G. A. Ávilla, Leila Grisa, Airton Aranha, Karina C. F. Tosin, Karin R. P. Ogradowski, Geneci Lima, Edith F. Legal, Tania H. Anegawa, Tânia L. Mazzuco, André L. Grion, José H. G. Balbinotti, Karin L. Dammski, Rosiane G. Melo, Nilton Kiesel Filho, Gislaine Custódio and Bonald C. Figueiredoadd Show full author list remove Hide full author list
Cancers 2019, 11(11), 1804; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111804 - 16 Nov 2019
Cited by 13 | Viewed by 3772
Abstract
The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 [...] Read more.
The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

13 pages, 3354 KiB  
Article
Antineoplastic Effect of a Combined Mitotane Treatment/Ionizing Radiation in Adrenocortical Carcinoma: A Preclinical Study
by Lidia Cerquetti, Barbara Bucci, Giulia Carpinelli, Pina Lardo, Antonella Proietti, Raffaele Saporito, Guido Rindi, Elisa Petrangeli, Vincenzo Toscano and Antonio Stigliano
Cancers 2019, 11(11), 1768; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111768 - 09 Nov 2019
Cited by 10 | Viewed by 2509
Abstract
Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in adrenal cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, [...] Read more.
Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in adrenal cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, we used mouse xenografts bearing human ACC to test the effects of MTT and IR alone and in combination. We evaluated tumor growth inhibition by the RECIST criteria and analyzed the cell cycle by flow cytometry (FCM). In the xenograft ACC model treated with MTT/IR in combination, we observed a marked inhibition of tumor growth, with strong tumor regression (p < 0.0001) compared to MTT and IR given alone (p < 0.05). The MTT results confirm its antisteroidogenic activity (p < 0.05) in the xenograft ACC model, revealing its ability to render cancer cells more prone to radiotherapy treatment. In addition, to explain the biological effect of these treatments on the Mismatch Repair System (MMR), we interfered with the MSH2 gene expression in untreated and MTT/IR-treated H295R and SW13 cell lines. Moreover, we observed that upon treatment with MTT/IR to induce DNA damage, MSH2 gene inhibition in both the H295R and SW13 cell lines did not allow DNA damage repair, thus inducing cell death. In conclusion, MTT seems to have a radiosensitizing property and, when given in combination with IR, is able to promote neoplastic growth inhibition, leading to a significant reduction in tumor size due to cell death. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

16 pages, 4962 KiB  
Article
The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score
by Ivy Zortéa S. Parise, Guilherme A. Parise, Lúcia Noronha, Mirvat Surakhy, Thiago Demetrius Woiski, Denise B. Silva, Tatiana EI-Jaick B. Costa, Maria Helena C. P. Del-Valle, Heloisa Komechen, Roberto Rosati, Melyssa Grignet Ribeiro, Marilza Leal Nascimento, José Antônio de Souza, Diancarlos P. Andrade, Mariana M. Paraizo, Marjorana Martini R. Galvão, José Renato S. Barbosa, Miriam Lacerda Barbosa, Gislaine C. Custódio, Mirna M. O. Figueiredo, Ana Luiza M. R. Fabro, Gareth Bond, Marco Volante, Enzo Lalli and Bonald C. Figueiredoadd Show full author list remove Hide full author list
Cancers 2019, 11(11), 1730; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111730 - 05 Nov 2019
Cited by 22 | Viewed by 3055
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

21 pages, 1536 KiB  
Review
Past, Present and Future of Epigenetics in Adrenocortical Carcinoma
by Madeleine Ettaieb, Thomas Kerkhofs, Manon van Engeland and Harm Haak
Cancers 2020, 12(5), 1218; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12051218 - 13 May 2020
Cited by 22 | Viewed by 3162
Abstract
DNA methylation profiling has been suggested a reliable technique to distinguish between benign and malignant adrenocortical tumors, a process which with current diagnostic methods remains challenging and lacks diagnostic accuracy of borderline tumors. Accurate distinction between benign and malignant adrenal tumors is of [...] Read more.
DNA methylation profiling has been suggested a reliable technique to distinguish between benign and malignant adrenocortical tumors, a process which with current diagnostic methods remains challenging and lacks diagnostic accuracy of borderline tumors. Accurate distinction between benign and malignant adrenal tumors is of the essence, since ACC is a rare but aggressive endocrine disease with an annual incidence of about 2.0 cases per million people per year. The estimated five-year overall survival rate for ACC patients is <50%. However, available treatment regimens are limited, in which a radical surgical resection is the only curable option. Nevertheless, up to 85% of patients with radical resection show recurrence of the local disease often with concurrent metastases. Adrenolytic therapy with mitotane, administered alone or in combination with cytotoxic agents, is currently the primary (palliative) treatment for patients with advanced ACC and is increasingly used in adjuvant setting to prevent recurrence. Prognostic stratification is important in order to individualize adjuvant therapies. On April 1, 2020, there were 7404 publications on adrenocortical carcinoma (adrenocortical carcinoma) OR adrenocortical carcinoma [MeSH Terms]) OR adrenal cortex cancer[MeSH Terms]) OR adrenal cortical carcinoma [MeSH Terms]) OR adrenal cortex neoplasm [MeSH Terms]) OR adrenocortical cancer [MeSH Terms]), yet the underlying pathophysiology and characteristics of ACC is not fully understood. Knowledge on epigenetic alterations in the process of adrenal tumorigenesis is rapidly increasing and will add to a better understanding of the pathogenesis of ACC. DNA methylation profiling has been heralded as a promising method in the prognostication of ACC. This review summarizes recent findings on epigenetics of ACC and its role in diagnosis, prognosis and therapeutic strategies. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

12 pages, 423 KiB  
Review
Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions
by Sara Bedrose, Marilyne Daher, Lina Altameemi and Mouhammed Amir Habra
Cancers 2020, 12(2), 508; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12020508 - 22 Feb 2020
Cited by 33 | Viewed by 5223
Abstract
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation [...] Read more.
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

17 pages, 544 KiB  
Review
Non-Coding RNAs in Adrenocortical Cancer: From Pathogenesis to Diagnosis
by Abel Decmann, Pál Perge, Peter Istvan Turai, Attila Patócs and Peter Igaz
Cancers 2020, 12(2), 461; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12020461 - 17 Feb 2020
Cited by 15 | Viewed by 2457
Abstract
Non-coding RNA molecules including microRNAs and long non-coding RNAs (lncRNA) have been implicated in the pathogenesis of several tumors and numerous data support their applicability in diagnosis as well. Despite recent advances, the pathogenesis of adrenocortical cancer still remains elusive and there are [...] Read more.
Non-coding RNA molecules including microRNAs and long non-coding RNAs (lncRNA) have been implicated in the pathogenesis of several tumors and numerous data support their applicability in diagnosis as well. Despite recent advances, the pathogenesis of adrenocortical cancer still remains elusive and there are no reliable blood-borne markers of adrenocortical malignancy, either. Several findings show the potential applicability of microRNAs as biomarkers of malignancy and prognosis, and there are some data on lncRNA as well. In this review, we present a synopsis on the potential relevance of non-coding RNA molecules in adrenocortical pathogenesis and their applicability in diagnosis from tissue and blood. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

13 pages, 393 KiB  
Review
Health-Related Quality of Life in Adrenocortical Carcinoma
by Rebecca V. Steenaard, Laura A. Michon and Harm R. Haak
Cancers 2019, 11(10), 1500; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11101500 - 08 Oct 2019
Cited by 11 | Viewed by 2722
Abstract
Insight into the health-related quality of life (HRQoL) impact of adrenocortical carcinoma (ACC) is important. The disease and its treatment options potentially have an impact on HRQoL. For patients with limited survival, HRQoL research is of utmost importance. We will therefore provide an [...] Read more.
Insight into the health-related quality of life (HRQoL) impact of adrenocortical carcinoma (ACC) is important. The disease and its treatment options potentially have an impact on HRQoL. For patients with limited survival, HRQoL research is of utmost importance. We will therefore provide an overview of HRQoL studies in patients with ACC. We found six studies that measured HRQoL in 323 patients with ACC (3 cross-sectional, 1 cohort, 2 trials), all indicating a reduced HRQoL compared to the general population. The FIRMACT trial found that HRQoL of patients with ACC was reduced compared to the general population, and that chemotherapy-mitotane further reduced HRQoL even though survival improved. Clinical aspects of the disease, including cortisol and aldosterone production and adrenal insufficiency have shown great impact on HRQoL in benign disease, even after the recovery of hormonal status. However, the impact of malignant adrenal disease and treatment options on HRQoL including adrenalectomy, radiotherapy, mitotane therapy, and chemotherapy have not been sufficiently studied in patients with ACC. Although the number of HRQoL studies in patients with ACC is limited, the existing literature does indicate that ACC has a large impact on patients’ HRQoL, with disease specific aspects. Further HRQoL research in patients with ACC is essential to improve patient-centered care, preferably by using an ACC-specific HRQoL questionnaire. Full article
(This article belongs to the Special Issue Adrenocortical Carcinoma)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-23
Back to TopTop