Please use this identifier to cite or link to this item: https://doi.org/10.25143/prom-rsu_2021-04_dts
Title: Immunohistochemical classification of diffuse gliomas. Summary of the Doctoral Thesis
Other Titles: Difūzo gliomu imūnhistoķīmiskā klasifikācija. Promocijas darba kopsavilkums
Authors: Štrumfa, Ilze
Gardovskis, Jānis
Jakovļevs, Arvīds
Keywords: Summary of the Doctoral Thesis
Issue Date: 2021
Publisher: Rīga Stradiņš University
Citation: Jakovļevs, A. 2021. Immunohistochemical classification of diffuse gliomas: Summary of the Doctoral Thesis: Sub-Sector – Pathology. Rīga: Rīga Stradiņš University. https://doi.org/10.25143/prom-rsu_2021-04_dts
Abstract: Glioblastoma (GBM) is one of the most common and aggressive tumours of the central nervous system (CNS) and represents the highest grade (grade IV) of glioma. Despite the standard therapy with maximal possible resection, followed by radiotherapy and chemotherapy with temozolomide, the prognosis for GBM patients remains dismal. Identification and research of potential molecular and immunohistochemical markers will help to increase our awareness of critical molecular changes in tumorigenesis and increase the possibility of effective molecularly targeted therapy in future. New molecular and immunohistochemical prognostic markers can improve the treatment and even allow patients to be stratified into different prognostic groups, which will make the therapy more personalized. The aim of this research was to evaluate the morphological and immunohistochemical profile of gliomas ? glioblastoma (GBM) and diffuse astrocytoma (DA) ? as well as to evaluate the prognostic role of single immunohistochemical markers and the possibility of glioma subtyping by immunohistochemistry (IHC). This work was performed as a retrospective study that is based on the analysis of formalin-fixed, paraffin-embedded, surgically treated human glioma tissues. In the study, a comprehensive morphological and immunohistochemical evaluation was performed including analysis of eight immunohistochemical parameters and survival analysis by applying a wide range of descriptive and analytic statistic methods. A total of 172 patients with gliomas were enrolled in the research work, including 146 GBMs and 26 DAs. It was found that GBM patients were characterized by poor prognosis with a median survival time of 7.9 months, which is slightly below the survival rates reported in other countries. From the selected markers, the presence of isocitrate dehydrogenase 1 (IDH1) R132H mutation was the most significant prognostic factor of better survival in gliomas. However, in patients with DAs, high platelet-derived growth factor receptor alpha (PDGFRA) expression was also associated with significantly better survival. Some immunohistochemical markers, such as CD44, p21, p27, PDGFRA and Ki-67 proliferation, are grade-specific parameters in gliomas, thus CD44, Ki-67 and p21 are significantly upregulated; however, p27 and PDGFRA are downregulated in high-grade gliomas such as GBM. Surprisingly, gender-related differences were found in the expression of some immunohistochemical markers, such as p27, CD44 and Ki-67, in gliomas. In GBMs, cell cycle proteins, such as p53, p21 and p27, are involved in a variety of mechanisms that regulate proliferation and angiogenesis. A strong relationship was also found between the expression of PDGFRA and p53 in gliomas. In DAs, PDGFRA correlated inversely with CD44, p21 and microvascular density (MVD). Finally, it was found that subtyping of gliomas is possible by IHC using a limited number of markers – PDGFRA, p53, IDH1, R132H and CD44. In addition, the expression of CD44 was shown to be a reliable indicator of mesenchymal subtype in GBM, which has a worse response to radiotherapy.
Description: The Doctoral Thesis was developed at Rīga Stradiņš University, Latvia. Defence: at the public session of the Promotion Council of the Basic Sciences of Medicine, including Pharmacology on 10th June, 2021 at 12.00 remotely via Zoom online meeting.
DOI: https://doi.org/10.25143/prom-rsu_2021-04_dts
License URI: http://creativecommons.org/licenses/by-nc/4.0/
Appears in Collections:2021. gadā aizstāvētie promocijas darbi un kopsavilkumi

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