Clinical Neuroscience

Wnt pathway markers in low-grade and high-grade gliomas

NAGY Ádám1, TOMPA Márton2, KRABÓTH Zoltán2, GARZULY Ferenc 3, MARÁCZI Alexandra 1, KÁLMÁN Bernadette2,1

SEPTEMBER 30, 2021

Clinical Neuroscience - 2021;74(09-10)

DOI: https://doi.org/10.18071/isz.74.0349

Journal Article

Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes. Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations. In the normal brain – grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas. These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.

AFFILIATIONS

  1. Department of Molecular Pathology, Markusovszky University Teaching Hospital, Szombathely
  2. Institute of Laboratory Medicine, Clinical Center and the Szentagothai Research Center, University of Pécs, School of Medicine, Pécs
  3. Department of Pathology, Markusovszky University Teaching Hospital, Szombathely

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[Is the implementation of Vojta therapy associated with faster gross motor development in children with cerebral palsy? ]

SANZ-MENGIBAR Jose Manuel , MENENDEZ-PARDIÑAS Monica , SANTONJA-MEDINA Fernando

[Vojta therapy has been reported as clinically beneficial for strength, movement and gross motor activities in individual cases and is being included within the second of three levels of evidence in interventions for cerebral palsy. The goal of this study is to understand the effect of Vojta therapy on the gross motor function. Our clinical trial followed a one group, pre-post design to quantify rates of changes in GMFM-88 after a two-months period undergoing Vojta therapy. A total of 16 patients were recruited. Post-intervention acceleration rates of GMFM-88-items acquisition (0.005; p<0.001) and Locomotor Stages (1.063; p<0.0001) increased significatively following Vojta the­rapy intervention. In this study, Vojta therapy has shown to accelerate the acquisition of GMFM-88-items and Loco­motor Stages in children with cerebral palsy younger than 18 months. Because functional training was not utilised, and other non-Vojta therapy intervention did not influence the outcome, Vojta therapy seems to activate the postural control required to achieve uncompleted GMFM-88-items. ]

Clinical Neuroscience

[Treatment and new evidences in neuromyelitis optica spectrum disorder ]

ILLÉS Zsolt

[Treatment and new evidences in neuromyelitis optica spectrum disorder Illés Zs, MD, PhD Ideggyogy Sz 2021;74(9–10):309–321. Neuromyelitis optica spectrum disorder (NMOSD) is associated with antibodies against AQP4 in about 80% of the cases. In about one-fourth of seronegative cases, antibodies against the MOG protein are present in the serum (MOG-antibody associated disease, MOGAD). This article discusses off-label azathioprine and mycophenolate mofetil in the treatment of NMOSD and reviews the evidence-based clinical aspects of B/plasma cell depletion, antagonization of IL-6 signaling and blocking the complement pathway. The review also summarizes basic aspects of NMOSD pregnancy focusing on treatment, and the different therapeutic approach in MOGAD. In the recent two years, phase 3 clinical trials provided class I evidence for the efficacy and safety of rituximab (anti-CD20), inebilizumab (anti-CD19), tocilizumab (anti-IL6R), satralizumab (anti-IL6R), and eculizumab (anti-C5) in combination with other immunosuppressants or in monotherapy. The treatment approach in MOGAD is complicated by the monophasic course in about half of the cases and by the potential disappearance of MOG antibody. The necessity of maintenance treatment in MOGAD should be decided after tapered oral steroid. Immunosuppression is recommended in NMOSD during pregnancy and lactation, and this should be considered for optimal selection of treatment in fertile female patients. The new monoclonal antibodies broadened treatment options NMOSD, and the treatment strategy of MOGAD has become more straightforward.]

Clinical Neuroscience

Chronic form of Pisa syndrome after prolonged exposure to low-dose amisulpride treatment

ERDEM Şimşek Nazan, ÖZKAYNAK Sibel Sehur

Pisa syndrome is a movement problem defined by tonic, sustained lateral flexion with a slight posterior rotation of the trunk. It seems to be a side effect of antipsychotic medicine in most cases. The clinical duration of Pisa syndrome can be acute, chronic, or recurrent. As far as we know, no reports are available in the literature on the chronic form of Pisa syndrome caused by low-dose amisulpride. A case of refractory tardive dystonia form of Pisa syndrome during treatment with stable low-dose amisulpride is presented in this report. Long-term, low-dosage amisulpride therapy may induce tardive dystonia even in patients with no other risk factors for dystonia.

Clinical Neuroscience

Medication overuse headache: The effectivity of iv lidocaine – magnesium

TEPE Nermin, TERTEMIZ Faysal Oktay

The detoxification process in medication overuse headache is the most difficult process for the patient. We aimed to investigate the effectiveness of the combination of low dose IV lidocaine and magnesium (100 mg lidocaine and 1.25 mg magnesium) in patients with medication overuse headache during the detoxification process. A total of 30 patients were included in the study; 15 received 24 hours of IV hydration, 15 received 1-hour lidocaine-magnesium infusion at the onset of pain in addition to the 24 hours of IV hydration. Headache severity (numeric rating scale, NRS), attack durations, onset of headache, monthly analgesic/triptan intakes, numbers of monthly headache days data were documented. We evaluated the severity of headache before and after daily treatment of two groups for one week. When both groups were compared, there was no significant difference in the pre-treatment NRS values, whe­reas, in the group receiving IV lidocaine-magnesium combination, there was a statistically significant decrease in the post-treatment NRS values in the first five days (p <0.05). An 1-hour combined infusion of lidocaine-magnesium may be considered as an alternative option for the patient to have a more quality detoxification process during the hospital stay, so that in parallel to the reduction in the use of multiple treatments (such as neuroleptics, benzodiazepines, antiemetics and opioids) and duration length of stay, the economic costs can also be reduced. The administration of combination will bring fewer side effects compared to their administration separately.

Clinical Neuroscience

[Mentalizing deficit among patients with traumatic brain injury ]

TAMÁS Viktória, BÜKI András, HEROLD Róbert

[Mentalization or theory of mind as an aspect of our social cognition, is our ability to infer mental states of others (intentions, desires, thoughts, emotions) and to predict their behavior accordingly. This function significantly affects our participation and orientation in the social world and plays an important role in conversational situations, social interactions, social integ­ration and adaptation. The brain regions that serve as the basis for mind-reading function can be damaged as a consequence of traumatic brain injury, which frequently occurs among the younger population. Traumatic brain injury can cause focal or diffuse cerebral injuries, often leading to theory of mind deficit. In this topic such publications were researched that compared theory of mind ability between traumatic brain injury patients and control subjects (comparative case-control studies). We searched for the studies in the following internet based/online databases: PubMed, Web of Science, ScienceDirect, Google Scholar, APA PsycNET (PsycARTICLES) and EBSCO Host. The search was performed using the following key word combinations: theory of mind or mentalizing or social cognition AND traumatic brain injury or head/brain injury or diffuse axonal injury. Based on the results of the included and processed studies (21 pc), traumatic brain injury often leads to mentalization deficit with different severity. With this present review we aim to draw attention to the fact that the appearance and severity of mind reading dysfunction can considerably affect the outcome of the disease, the length of rehabilitation time and the prognosis of traumatic brain injury patients. Besides this, with this review, we aim to take sides in whether theory of mind ability is domain-specific or domian-general based on studies including traumatic brain injury patients.]

All articles in the issue

Related contents

Clinical Neuroscience

[Role of the intraoperative electrical brain stimulation in conserving the speech and language function in neurosurgical operations of awake patients]

ERÕSS Loránd, FEKETE Gábor, ENTZ László, FABÓ Dániel, BORBÉLY Csaba, KOZÁK Lajos Rudolf, ANDREJKOVICS Mónika, CZIRJÁK Sándor, FEDORCSÁK Imre, NOVÁK László, BOGNÁR László

[Aim of the study - To summarize the results gained with awake craniotomies, which were performed in either low grade glioma patients or epilepsy surgical patients whose tumor or epileptogenic zone, was in the vicinity of eloquent, mostly language, cortices. Patient selection and methods - In our retrospective study we selected 16 patients who were operated awake between 1999-2011 at the Neurosurgical Department of MÁV Kórház Budapest, or at the National Institute of Neurosciences in Budapest, or at the Neurosurgical Department of the University of Debrecen in Debrecen. In the presurgical evaluation if it was possible we performed functional magnetic resonance imaging, tractography and detailed neuropsychological testing. At the National Institute of Neurosciences all patients were operated with the aid of MR guided neuronavigation. Results - Anesthesia was carried out without complications in all of the 16 cases. Monitoring of sleep deepness has significantly contributed to the safety of anesthesia during the superficial anesthezied states of the operation. The intraoperative neuropsychological tasks used for testing language were sensitive enough to judge the little disturbances in speech during stimulation. Stimulation evoked seizures could be adequately managed during surgery and did not influence the outcome of the procedures. The use of neuronavigation helped significantly by planning the optimal place for the craniotomy and by intraoperative orientation. Conclusions - Awake craniotomies require well practiced surgical teams, which requires the cooperation of neuro-anesthesiologits, neurosurgeons, neuropsychologist and electrophysiologists. It has two goals, first to reduce the time of surgery to minimize surgical complications, secondly the detailed intraoperative mapping of cognitive and motor functions to avoid any neurological deficit. The intraoperative anatomical data provided by the neuronavigation and the functional data provided by awake intraoperative stimulation of the patient together serve the safety of the patient which is essential in the neurologically minimal invasive neurosurgical approach of the 21st century.]

Clinical Neuroscience

[Prognosis of neuroepithelial tumours by means of cell proliferation studies]

GYÖMÖRI Éva, MÉSZÁROS István, MÉHES Gábor, DÓCZI Tamás, PAJOR László

[Cell-kinetic analysis of tumours has recently been widely used in clinical oncology for prognosis of patients treated with malignant neoplasms and for controlling the efficiency of treatment protocols. Definition of biological nature of neuroepithelial tumours was based on grading depending on the severity of cellular anaplasia. Neuroepithelial tumours can be characterized not only by the histological features but also by the DNA content and abnormalities of the cell proliferation – though the relationship between histological malignancy, proliferative activity and cellular aneuploidity was found to be rather controversial according to the literature. In this review article the clinical value of cell cycle analysis such as distribution of DNA content, DNA index; S-phase fraction; proliferation-markers [MIB 1 antibody, bromdeoxy uridin labelling index, mitotic index, definition of nucleolar organization region) are discussed on the basis of personal experience and review of the appropriate literature. Flow cytometry and examination of proliferation markers have a significant role in the definition of prognosis of patients suffering from WHO grade II and III neuroepithelial tumours. Gliomas giving rise to recidivism have a rapid cell cycle already at their first occurrence, which is characterized by raised proliferation indices, and occurrence of aneuploid cell clones. An unfavourable outcome can be prognosed in patients suffering from a WHO grade II or III glioma if the DNA index is above or below 1+0.1 if the value of the S phase fraction is above 6%, if more than 1 mitosis is found in 10 large magnification field, and if the number of cells labelled with MIB 1 antibody exceeds 3 in 1 large magnification field. The literature confirms our notion that further studies of proliferation characteristics may help in the production of a malignity score of gliomas that could support the efficiency of traditional histological grading in prognosis and control of complex therapy of these tumours.]

Clinical Neuroscience

[Volumetric changes following 125 I interstitial irradiation of low grade gliomas]

JULOW Jenő, VIOLA Árpád, MAJOR Tibor, MANGEL László, BAJZIK Gábor, REPA Imre, SÁGI Sarolta, VALÁLIK István, EMRI Miklós, TRÓN Lajos, NÉMETH György

[Background - Image fusion permits quantitative analysis of the consequences of 125 Iodine interstitial irradiation of brain tumors. The volume of tumor necrosis, reactive zone and edema can be compared to the dosimetric data. Patients and method - Nineteen patients with low grade glioma were analyzed on the average 14.5 months following 125 Iodine interstitial irradiation. Dose planning and image fusion were performed with the Target 1.19 (BrainLab) software. The CT/MR images showing the so called “triple ring” (necrosis, reactive ring and edema) developing after the interstitial irradiation of brain tumors were fused with the planning images and the isodose curves. The volume of the three regions was measured. Values at the intersections of isodose curves and necrosis borders were averaged and used for calculation of tumor necrosis. The volume of normal brain tissue irradiated by given dose values, as well as homogeneity and conformality indices were also determined. Results - The relative volumes of the different parts of the “triple-ring” compared to the reference dose volume were the following: necrosis 54.9%, reactive zone 59.7%, and edema 445.3% . Tumor necrosis developed at 71.9 Gy dose. At the irradiation of an average size glioma with a volume of 12.7 cm3, 5 to 7 cm3 normal brain tissue around the tumor received 60-70 Gy dose. The average homogeneity and conformality indices were 0.24 and 0.57, respectively. Conclusion - The analysis of changes in the volume of edema, reactive ring and necrosis caused by interstitial irradiation, and their correlation with the dozimetric data using the image fusion method provide useful information for patient follow-up, clinical management and further therapeutic decisions.]

Clinical Neuroscience

[Identification of gliomas by morphological and immunocytochemical analysis in cell cultures]

FAZEKAS Ilona, KEREKES Edit, HEGEDŰS Balázs, NYÁRY István

[Introduction - The morphology and immunocytochemical properties of 250 different monolayer cultures derived from various human brain tumor specimens were investigated on purpose to support and complement the neuropatholgical diagnosis. In this study analyses of 124 glioma cases are presented. Methods - The tumor samples were mechanically dissociated and seeded on glass coverslips. After the formation of the monolayer cultures were fixed and stained by May-Grünwald- Giemsa method for the morphological examination. Semi-quantitative immunocytochemical labeling included several different types of mono- and polyclonal primary antibodies using avidin-biotin visualization system. In nine cases of the glioblastomas the sufficient proliferation made possible to establish cell lines from the primary cultures. Results - The glial origin of the tumors was identified in 124 cases based upon the presence of glial fibrillary acidic protein. A negative correlation between the intensity of glial fibrillary acidic protein immunostaining and the grade of tumor malignancy was found. During long-term cultivation of the higher grade gliomas the incidence and intensity of glial fibrillary acidic protein labeled cells was decreasing. Both the vimentin and the neuron specific enolase labeling were in general stronger than the glial fibrillary acidic protein and almost all the cells were stained. The incidence of Ki-67 positive cells increased with the grade of malignancy. Concerning the tumor classification our immunocytochemical results correlated with the routine histopathological examination. Conclusions - On the basis of these results we conclude that monolayer cultures obtained from tumor specimens can support and complement the correct diagnosis of the various human brain tumors.]

Clinical Neuroscience

[Evaluation of gliomas by means of multi-model techniques]

BORBÉLY Katalin

[Gliomas constitute more than 50% of brain tumours. Primary malignant forms recur within 1/2 to 1 year after surgery, and even totally removed benign forms may recur. 50% of recurrent astrocytomas are more malignant than the original tumour. The time elapsing until recurrence strongly depends on the degree of malignity and the surgical removal. However, the age of the patient also plays an important role. Survival of the patient after the establishment of diagnosis also depends on the therapy. Effective treatment requires a knowledge of the degree of malignity as well as differentiation between recurrent tumour and radiation necrosis. CT and MRI scans offer high sensitivity, but poor specificity. Evaluation of tumour metabolism by means of 18F-fluoro-deoxy-glucose positron emission tomography (PET-FDG) helps to determine the degree of malignity of the gliomas, and recurrent tumour can safely be differentiated from necrosis following radiation therapy.]