Immunohistochemically characterized intratumoral heterogeneity is a prognostic marker in human glioblastoma
Liesche-Starnecker F, Mayer K, Kofler F, Baur S, Schmidt-Graf F, Kempter J, Prokop G, Pfarr N, Wei W, Gempt J, Combs SE, Zimmer C, Meyer B, Wiestler B, Schlegel J (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 12
Pages Range: 1-17
Article Number: 2964
Journal Issue: 10
Abstract
Tumor heterogeneity is considered to be a hallmark of glioblastoma (GBM). Only more recently, it has become apparent that GBM is not only heterogeneous between patients (intertumoral heterogeneity) but more importantly, also within individual patients (intratumoral heterogeneity). In this study, we focused on assessing intratumoral heterogeneity. For this purpose, the heterogeneity of 38 treatment-naïve GBM was characterized by immunohistochemistry. Perceptible areas were rated for ALDH1A3, EGFR, GFAP, Iba1, Olig2, p53, and Mib1. By clustering methods, two distinct groups similar to subtypes described in literature were detected. The classical subtype featured a strong EGFR and Olig2 positivity, whereas the mesenchymal subtype displayed a strong ALDH1A3 expression and a high fraction of Iba1-positive microglia. 18 tumors exhibited both subtypes and were classified as “subtype-heterogeneous”, whereas the areas of the other tumors were all assigned to the same cluster and named “subtype-dominant”. Results of epigenomic analyses corroborated these findings. Strikingly, the subtype-heterogeneous tumors showed a clearly shorter overall survival compared to subtype-dominant tumors. Furthermore, 21 corresponding pairs of primary and recurrent GBM were compared, showing a dominance of the mesenchymal subtype in the recurrent tumors. Our study confirms the prognostic impact of intratumoral heterogeneity in GBM, and more importantly, makes this hallmark assessable by routine diagnostics.
Involved external institutions
Germany (DE)How to cite
APA:
Liesche-Starnecker, F., Mayer, K., Kofler, F., Baur, S., Schmidt-Graf, F., Kempter, J.,... Schlegel, J. (2020). Immunohistochemically characterized intratumoral heterogeneity is a prognostic marker in human glioblastoma. Cancers, 12(10), 1-17. https://doi.org/10.3390/cancers12102964
MLA:
Liesche-Starnecker, Friederike, et al. "Immunohistochemically characterized intratumoral heterogeneity is a prognostic marker in human glioblastoma." Cancers 12.10 (2020): 1-17.
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