Abstract
AimsGlioblastoma (GBM) is the most common and lethal malignant brain tumor in adults. Glioma stem cells (GSCs) are implicated in this poor prognosis and in radio(chemo‐)resistance. We have previously demonstrated that among potentially highly specific GSC markers oligodendrocyte lineage transcription factor 2 (OLIG2) appears to be the most specific and cyclin D2 (CCND2) the only one related to cell cycle regulation. The purpose of this work was to investigate the clinical significance and the evolution of OLIG2 and CCND2 protein expression in GBM.Methods and resultsImmunohistochemical expression analysis of Olig2 and Ccnd2 was carried out on a cohort of human paired GBM samples comparing initial resections with local recurrent tumors after radiation therapy (RT) alone or radio‐chemotherapy with temozolomide (RT‐TMZ). Uni‐ and multivariate logistic regression analysis revealed that significant risk factors predicting early mortality (<12 months) are: subtotal surgery for recurrence, time to recurrence <6 months, Ccnd2 nuclear expression at initial surgery ≥30%, and Olig2 nuclear expression <30% at second surgery after RT alone and RT‐TMZ.ConclusionsWe demonstrated that patients for whom nuclear expression of Olig2 becomes low (<30%) after adjuvant treatments have a significantly shorter time to recurrence and survival reflecting most probably a proneural to mesenchymal transition of the GSCs population. We also highlighted the fact that at initial surgery, high nuclear expression (≥30%) of CCND2, a G1/S regulator specific of GSCs, has a prognostic value and is associated with early mortality (<12 months).
Highlights
Glioblastoma (GBM) (World Health Organization [WHO] grade IV glioma) is the most common and lethal malignant brain tumor in adults.[1]
2016 WHO classification integrates to histological features the isocitrate dehydrogenase (IDH) mutation status, one of the most important genetic alterations found in GBM, as the few IDH‐mutant present a more favorable prognosis.[1]
Other studies showed that PN to MES transition is associated with global multidrug resistance.[16,17,44,55]. All these data could explain the poor prognosis associated with the decrease in Olig[2] expression that we showed in GBM after adjuvant treatments
Summary
Glioblastoma (GBM) (World Health Organization [WHO] grade IV glioma) is the most common and lethal malignant brain tumor in adults.[1]. | 1070 in surgical and radio‐chemotherapeutics treatments and the multiplicity of clinical trials testing new therapies without major success so far,[2] GBM remains incurable with a median survival of only 12‐18 months[3] and up to 31 months for IDH‐ mutant.[4] Several factors could contribute to this poor prognosis; the most important appears to be related to the presence of a population of radio/chemoresistant cells with stem‐like properties.[5,6,7,8] The glioma stem cells (GSCs) subpopulation is capable of self‐renewal, persistent proliferation, dedifferentiation, multipotency and has the ability to be highly tumorigenic allowing for tumor regrowth after standard treatments.[9] developing additional therapeutic strategies targeting and eliminating the GSCs component is crucial to one day render GBM curable. The purpose of this work was to investigate by immunohistochemistry (IHC) the clinical significance and the evolution of OLIG2 and CCND2 protein expression on a cohort of human paired GBM samples comparing initial resections with recurrent tumors after radiation therapy (RT) alone or radio‐chemotherapy with temozolomide (RT‐TMZ) according to the Stupp regimen.[3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
