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Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to...
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Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 15418

Special Issue Editor

Dr. Guillaume Gauchotte

E-Mail Website
Guest Editor
Departement of Biopathology - Anatomie et Cytologie Pathologiques, CHRU Nancy, Institut de Cancérologie de Lorraine Institut Médico-Légal de Nancy, 54000 Nancy, France
Interests: meningioma; glioma; forensic; immunohistochemistry; histopathology

Special Issue Information

Dear Colleagues,

To date, brain tumors are often still life-threatening pathologies. Among these, meningiomas and glioblastoma are the most frequent histopathological types, with limited therapeutical options and heterogeneous prognosis and response to adjuvant treatments. There is a critical need to identify new prognostic and predictive markers in these tumors.

In this Special Issue, the authors will focus on molecular and histopathological features of brain tumors, from physiopathological insights to clinico-pathological applications and the identification of new potential therapeutical targets. It may be based on preclinical models as well as clinical series, with various methods, such as cell culture and transfection, histology, image analysis, immunohistochemistry, PCR, transcriptomics, and methylome.

Dr. Guillaume Gauchotte
Guest Editor

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

  • neuropathology
  • brain tumors
  • meningioma
  • glioma
  • predictive marker
  • prognosis
  • methylome

Published Papers (7 papers)

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Research

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12 pages, 1745 KiB  
Article
p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances
by Lucas Geyer, Thibaut Wolf, Marie-Pierre Chenard, Helene Cebula, Roland Schott, Georges Noel, Eric Guerin, Erwan Pencreach, Damien Reita, Natacha Entz-Werlé and Benoît Lhermitte
Cancers 2023, 15(5), 1512; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051512 - 28 Feb 2023
Cited by 4 | Viewed by 1861
Abstract
CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to [...] Read more.
CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to which immunohistochemical levels of p16 expression may provide information about CDKN2A deletion. A retrospective study was conducted in 173 gliomas of all types, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess the prognostic impact of p16 expression and CDKN2A deletion on patient outcomes. Three patterns of p16 expression were observed: absence of expression, focal expression, and overexpression. Absence of p16 expression was correlated with worse outcomes. p16 overexpression was associated with better prognoses in MAPK-induced tumors, but with worse survival in IDH-wt glioblastomas. CDKN2A homozygous deletion predicted worse outcomes in the overall patient population, particularly in IDH-mutant 1p/19q oligodendrogliomas (grade 3). Finally, we observed a significant correlation between p16 immunohistochemical loss of expression and CDKN2A homozygosity. IHC has strong sensitivity and high negative predictive value, suggesting that p16 IHC might be a pertinent test to detect cases most likely harboring CDKN2A homozygous deletion. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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10 pages, 2345 KiB  
Article
A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals
by Guillaume Gauchotte, Charles Bédel, Emilie Lardenois, Sébastien Hergalant, Laura Cuglietta, Robin Pflaum, Stéphanie Lacomme, Héloïse Pina, Mathilde Treffel, Fabien Rech and Shyue-Fang Battaglia-Hsu
Cancers 2023, 15(2), 535; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15020535 - 16 Jan 2023
Cited by 1 | Viewed by 1747
Abstract
The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World [...] Read more.
The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (p = 0.004 and p = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (p = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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22 pages, 3567 KiB  
Article
Correlation between DNA Methylation and Cell Proliferation Identifies New Candidate Predictive Markers in Meningioma
by Sébastien Hergalant, Chloé Saurel, Marion Divoux, Fabien Rech, Celso Pouget, Catherine Godfraind, Pierre Rouyer, Stéphanie Lacomme, Shyue-Fang Battaglia-Hsu and Guillaume Gauchotte
Cancers 2022, 14(24), 6227; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246227 - 17 Dec 2022
Cited by 3 | Viewed by 2329
Abstract
Meningiomas are the most common primary tumors of the central nervous system. Based on the 2021 WHO classification, they are classified into three grades reflecting recurrence risk and aggressiveness. However, the WHO’s histopathological criteria defining these grades are somewhat subjective. Together with reliable [...] Read more.
Meningiomas are the most common primary tumors of the central nervous system. Based on the 2021 WHO classification, they are classified into three grades reflecting recurrence risk and aggressiveness. However, the WHO’s histopathological criteria defining these grades are somewhat subjective. Together with reliable immunohistochemical proliferation indices, other molecular markers such as those studied with genome-wide epigenetics promise to revamp the current prognostic classification. In this study, 48 meningiomas of various grades were randomly included and explored for DNA methylation with the Infinium MethylationEPIC microarray over 850k CpG sites. We conducted differential and correlative analyses on grade and several proliferation indices and markers, such as mitotic index and Ki-67 or MCM6 immunohistochemistry. We also set up Cox proportional hazard models for extensive associations between CpG methylation and survival. We identified loci highly correlated with cell growth and a targeted methylation signature of regulatory regions persistently associated with proliferation, grade, and survival. Candidate genes under the control of these regions include SMC4, ESRRG, PAX6, DOK7, VAV2, OTX1, and PCDHA-PCDHB-PCDHG, i.e., the protocadherin gene clusters. This study highlights the crucial role played by epigenetic mechanisms in shaping dysregulated cellular proliferation and provides potential biomarkers bearing prognostic and therapeutic value for the clinical management of meningioma. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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14 pages, 1608 KiB  
Article
Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH-Mutant Gliomas: A French POLA Network Study
by Coline Montégut, Jean-Sébastien Guillamo, François Ducray, Caroline Dehais, Elisabeth Cohen-Jonathan Moyal, Christine Desenclos, Antoine Petit, Romuald Seizeur, Lien Bekaert, Claude Gaultier, Marie Jeannette Motuo Fotso, Marie Blonski, Jean-Sébastien Frenel, Elodie Vauléon, Olivier Langlois, Georges Noel, Antoine F. Carpentier, Anna Luisa Di Stefano, Charlotte Bronnimann, Dominique Figarella-Branger, Olivier Chinot and Emeline Tabouretadd Show full author list remove Hide full author list
Cancers 2022, 14(22), 5509; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225509 - 09 Nov 2022
Cited by 2 | Viewed by 1258
Abstract
Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger [...] Read more.
Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (<70 years) and of elderly patients IDHwt HGG. Geriatric features were collected. Results: Out of 1433 HGG patients included, 119 (8.3%) were ≥70 years. Among them, 39 presented with IDHm HGG. The main characteristics of elderly IDHm HGG were different from those of elderly IDHwt HGG but similar to those of younger IDHm HGG. In contrast, their therapeutic management was different from those of younger IDHm HGG with less frequent gross total resection and radiotherapy. The median progression-free survival (PFS) and overall survival (OS) were longer for elderly patients IDHm HGG (29.3 months and 62.1 months) than elderly patients IDHwt HGG (8.3 months and 13.3 months) but shorter than those of younger patients IDHm HGG (69.1 months and not reached). Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, body mass index, and autonomy. Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, and body mass index, and autonomy. Conclusion: the outcome of IDHm HGG in elderly patients is better than that of IDHwt HGG. Geriatric assessment may be particularly important to optimally manage these patients. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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15 pages, 5990 KiB  
Article
Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling
by Alex Hirtz, Nolwenn Lebourdais, Magalie Thomassin, Fabien Rech, Hélène Dumond and Hélène Dubois-Pot-Schneider
Cancers 2022, 14(17), 4114; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174114 - 25 Aug 2022
Cited by 3 | Viewed by 1579
Abstract
Low-grade gliomas are rare primary brain tumors, which fatally evolve to anaplastic gliomas. The current treatment combines surgery, chemotherapy, and radiotherapy. If gender differences in the natural history of the disease were widely described, their underlying mechanisms remain to be determined for the [...] Read more.
Low-grade gliomas are rare primary brain tumors, which fatally evolve to anaplastic gliomas. The current treatment combines surgery, chemotherapy, and radiotherapy. If gender differences in the natural history of the disease were widely described, their underlying mechanisms remain to be determined for the identification of reliable markers of disease progression. We mined the transcriptomic and clinical data from the TCGA-LGG and CGGA databases to identify male-over-female differentially expressed genes and selected those associated with patient survival using univariate analysis, depending on molecular characteristics (IDH wild-type/mutated; 1p/19q codeleted/not) and grade. Then, the link between the expression levels (low or high) of the steroid biosynthesis enzyme or receptors of interest and survival was studied using the log-rank test. Finally, a functional analysis of gender-specific correlated genes was performed. HOX-related genes appeared to be differentially expressed between males and females in both grades, suggesting that a glioma could originate in perturbation of developmental signals. Moreover, aromatase, androgen, and estrogen receptor expressions were associated with patient survival and were mainly related to angiogenesis or immune response. Therefore, consideration of the tight control of steroid hormone production and signaling seems crucial for the understanding of glioma pathogenesis and emergence of future targeted therapies. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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Review

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13 pages, 1919 KiB  
Review
Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?
by Sergio Corvino, Giuseppe Mariniello, Giuseppe Corazzelli, Raduan Ahmed Franca, Marialaura Del Basso De Caro, Rosa Della Monica, Lorenzo Chiariotti and Francesco Maiuri
Cancers 2022, 14(14), 3464; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143464 - 16 Jul 2022
Cited by 3 | Viewed by 3407
Abstract
Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of [...] Read more.
Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. Methods: A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Results: Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. Conclusions: The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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Other

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17 pages, 5332 KiB  
Systematic Review
Hormone Receptor Expression in Meningiomas: A Systematic Review
by Mikaël Agopiantz, Mélanie Carnot, Constance Denis, Elena Martin and Guillaume Gauchotte
Cancers 2023, 15(3), 980; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030980 - 03 Feb 2023
Cited by 9 | Viewed by 2386
Abstract
Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature. Several studies have discussed the expression of progesterone, estrogen, androgen, and somatostatin receptors. The utility of analyzing these [...] Read more.
Meningiomas are, in most cases, low grade intracranial tumors. However, relapses are frequent. To date, only a few prognostic markers are described in the literature. Several studies have discussed the expression of progesterone, estrogen, androgen, and somatostatin receptors. The utility of analyzing these expressions for prognostic, theragnostic, and therapeutic purposes remains unclear. The aim of this study was to report the expression of these receptors, based on immunohistochemistry. Cochrane Collaboration guidelines and PRISMA statements were followed. We did an online search in PubMed using the MeSH database. References were selected if the investigations occurred from 1990 to 2022. 61 references were included (34 descriptive observational studies, 26 analytical observational studies, and one case report). In this review, we describe the expression of these receptors in function of age, sex, hormonal context, localization, histological subtype, grade, and recurrence. Full article
(This article belongs to the Special Issue Predictive and Prognostic Markers in Brain Tumors: From Physiopathology to Clinical Applications)
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