Clinical Neuroscience

[Occurence and molecular pathology of high grade gliomas]

MURNYÁK Balázs, CSONKA Tamás, HEGYI Katalin, MÉHES Gábor, KLEKNER Álmos, HORTOBÁGYI Tibor

OCTOBER 05, 2013

Clinical Neuroscience - 2013;66(09-10)

[Background - Glial tumours represent the most frequent type of primary brain cancers. Gliomas are characterized by heterogeneity that makes the diagnosis, histological classification and the choosing of correct therapy more difficult. Despite the advances in developing therapeutic strategies patients with malignant gliomas have a poor prognosis; therefore glial tumours represent one of the most important areas of cancer research. There are no detailed data on the epidemiology of gliomas in Hungary. Methods - In the first section of our publication, we analysed the histological diagnosed cases between 2007 and 2011 at the Institute of Pathology, University of Debrecen Medical and Health Science Centre. We analyzed the incidence of 214 high-grade gliomas by tumor grades, gender, age, and the anatomical localization. Results - The majority of cases were glioblastoma (182 cases), and the remaining 32 cases were anaplastic gliomas. The mean age of patients was 57 years (±16.4), and the male:female ratio was 1.1:1. The most frequent area of tumors was the frontal lobe followed by the temporal, parietal and occipital lobe. We include new findings published recently about glioma patogenesis, molecular pathways, mutant genes and chromosomal regions. We explain briefly the role of selected important genes in glioma genesis and give an update on knowledge provided by modern molecular methods, which could beneficially influence future therapy and the diagnosis of gliomas.]

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SZŰCS Anna, MAROSFŐI Miklós, VÁRALLYAY Péter, KAMONDI Anita

Clinical Neuroscience

[Occurence and molecular pathology of low grade gliomas]

MURNYÁK Balázs, CSONKA Tamás, KLEKNER Álmos, HORTOBÁGYI Tibor

[Background - The WHO grade I. and II. low-grade gliomas represent nearly the 15% of all primary brain tumors. These tumours contain clinically, hisologically and molecularly distinct tumor types. According to their histologic characteristic, grade II glial tumours are the diffuse astrocytoma, oligodendroglioma and oligoastrocytoma subgroups; the ependymal tumors are not included in this study. Methods - In our publication, we analysed the histological diagnosed glioma cases between 2007 and 2011 at our institution. Results - Low-grade gliomas were diagnosed in 127 cases (62 male / 65 female), and the mean ages were 39 years (±20.3). More than half of the cancers were localizated in the frontal lobe, and the second most frequent area was the temporal lobe. Finally, we comlete our report with an overview of major molecular pathways in low-grade gliomas.]

Clinical Neuroscience

[In memoriam Zoltán Várhegyi (1939. 01. 03-2012. 08. 10.)]

TÖRÖK Pál

Clinical Neuroscience

[Infection-surveillance experience at a neurological intensive care unit]

CSIMA Zoltán, HRADECZKY Katalin, SIMONNÉ SZAPPANOS Erzsébet, BERECZKI Dániel, SIPOS Ildikó

[Infection-surveillance is an important part of the infection control system serving the protection of patients and healthcare workers as well. The continuous surveillance of health care associated infections is among the most important fields of patient safety and quality management. The aim of this study was to evaluate the frequency of the health care associated infections among patients at the neurointensive care unit. Moreover, we aimed to identify specific infectionforms and the most frequently occurring pathogens. We performed the study for a half-year according to the HELICSmethod proposed by the National Center of Epidemiology. In this setup we evaluated the infections and risk factors for infection (instrument-use, antibiotic therapy etc.) among the patients who spent at least 48 hours in the neurointensive care unit. During the six-month period, we observed 16 health care associated mono- and polymicrobial infections out of the 88 cases. Mainly Gram-positive pathogens were identified, but we found multidrug-resistant pathogens as well. Clinically diagnosed pneumonia was the most frequent among the infections. These infections were detected by a relatively low microbiological testing rate, which warns to increase sampling frequency to ensure more accurate data on infections. Infection control based on a comparative standardized infection dataset seems to be one of the most important preventive measures.]

Clinical Neuroscience

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Clinical Neuroscience

[Occurence and molecular pathology of low grade gliomas]

MURNYÁK Balázs, CSONKA Tamás, KLEKNER Álmos, HORTOBÁGYI Tibor

[Background - The WHO grade I. and II. low-grade gliomas represent nearly the 15% of all primary brain tumors. These tumours contain clinically, hisologically and molecularly distinct tumor types. According to their histologic characteristic, grade II glial tumours are the diffuse astrocytoma, oligodendroglioma and oligoastrocytoma subgroups; the ependymal tumors are not included in this study. Methods - In our publication, we analysed the histological diagnosed glioma cases between 2007 and 2011 at our institution. Results - Low-grade gliomas were diagnosed in 127 cases (62 male / 65 female), and the mean ages were 39 years (±20.3). More than half of the cancers were localizated in the frontal lobe, and the second most frequent area was the temporal lobe. Finally, we comlete our report with an overview of major molecular pathways in low-grade gliomas.]

Clinical Oncology

[P53 – the suppressor]

KOPPER László

[Our basic nature requere cells quantity and quality to perform differenciate activity. p53 has the responsibility for quick out those cells who carries molecular failures in DNA avoiding transfer mutations into doughter cells. If the DNA-repair insuffi cient p53s with on apoptosis. Whe p53 is mutated the phenotypes are different in a wide range due to the heterogenity of the DNA damages, and also the expression pattern of a suppressor protein. With the increasing amout the damaged DNA the genomic instability elevates D the risk to development of tumors. It is linict mutated gene could be a promosing tr, 10t for therapy. So far the attempts have little value for the clinic.]

Clinical Oncology

[Molecular diagnostics of brain tumors - an up-date]

REINIGER Lilla, HANZÉLY Zoltán, BÁLINT Katalin, TURÁNYI Eszter

[In recent years there have been major advancements in the understanding of molecular events driving brain tumor genesis and progression. Although state-of-the-art techniques are not widely available, many of the molecular discoveries lead to novel antibodies that can assist in identifying the major molecular subgroups by immunohistochemistry. Molecular informations will likely be incorporated into the next World Health Organization (WHO) classifi cation of central nervous system tumors, but clinical practice in many centres have already taken on the available informations and therapeutic decisions are made based on genetic/epigenetic information. In the adult population IDH, ATRX and 1p/19q codeletion studies help to defi ne molecular subgroups that correlate better with prognosis and therapeutic response than traditional histology based diagnosis. The KIAA1549-BRAF fusion gene is a hallmark for pilocytic astrocytomas, while diffuse pediatric gliomas lack the IDH mutations and 1p/19q codeletions that are common in adult astrocytomas and oligodendrogliomas. Uncommon in adults, Histone H3.3 mutations are pathognomic in pediatric brainstem malignant gliomas. Molecular subgroups of medulloblastomas have also been identifi ed, and a corresponding set of antibodies are ready to guide treatment decisions in those centres where molecular techniques are not available. These genetic and epigenetic events determine a tumor’s behaviour, and integrating this level of informations into neuropathology practice is essential to provide the best possible care to both pediatric and adult patients.]

Clinical Neuroscience

Isocitrate dehydrogenase mutations in defining the biology of and supporting clinical decision making in glioblastoma

KÁLOVITS Ferenc, TOMPA Márton, NAGY Ádám, BERNADETTE Kalman

Background and purpose - Oncogenesis is related to a sequential accumulation of somatic mutations. Comprehensive characterizations of the genomic landscapes have been completed recently for several tumors, glioblastoma being among the first ones. Our own translational research studies have been focused on defining molecular subtypes of glioblastoma in the clinical setting because of an expected prognostic and therapeutic utility of the information. Somatic mutations in genes of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best-defined biomarkers that also influence tumor behavior and confer clinical utility. Methods - We have reviewed the literature including our own results to summarize basic science and clinical correlates of IDH mutations. Results - The surveyed data reveal genomic, transcriptomic, epigenomic and biochemical consequences of IDH mutations in the context of glioblastoma biology and phenotype. In addition, a few studies highlight the therapeutic potential of targeting IDH, although thus far all tests have only been conducted in the preclinical setting. Conclusions - Somatic mutations in isoforms of IDH genes represent important biomarkers that correlate with biochemical, biological and phenotypic features of glioblastoma, and may also facilitate the development of new therapeutic strategies complementing the currently available approved protocols.

Clinical Oncology

[Management of pancreatic cancer today]

BODOKY György, LAKATOS Gábor

[Pancreatic cancer (PC) is a major health problem with a poor prognosis. The number of patients with PC is increasing globally. There are no screening tests for early detection of PC, but even when diagnosed early, surgery is possible in only a minority of cases. Managing PC remains a big challenge. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging. In patients with resectable disease, adjuvant chemotherapy improves the fi ve year survival rate, whereas the use of adjuvant radiochemotherapy is still controversial. In metastatic cancer, monotherapy with gemcitabine remained the main therapeutic option during more than 10 years. Many different combinations with other drugs and new targeted therapies have been tested with gemcitabine. Only a combination of erlotinib and gemcitabine has shown a modest survival benefi t until now. Many gene alterations that directly contribute to pancreas tumorigenesis have been identifi ed or are under active investigation. Recently, the FOLFIRINOX regimen has been reported to be more active than gemcitabine in selected metastatic patients. Quality of life is an extremly important factor, when treating a patient with PC. CA 19-9 serum level can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. There is a strong need for other predictive biomarkers to select patients, who might benefi t from available and new therapeutic options.]