Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma

Abstract

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients’ survival suggests a prognostic role for this protein.

Ganglioside Composition Distinguishes Anaplastic Ganglioglioma Tumor Tissue from Peritumoral Brain Tissue: Complementary Mass Spectrometry and Thin-Layer Chromatography Evidence

“…The additional contribution of this study is the characterization of the ganglioside composition in valuable and rarely accessible peritumoral tissue since the important biochemical changes that occur within this area are considered responsible for tumor cell infiltration into the surrounding healthy brain tissue promoting tumor recurrence and possibly for tumor resistance to chemotherapeutic treatment [23,57].…”

Analysis of the Peritumoral Tissue Unveils Cellular Changes Associated with a High Risk of Recurrence

“…Second, the peritumoral tissue may contain infiltrating tumor cells that may later reseed the area. This model has been evidenced in cerebral tumors [ 22 , 23 , 24 , 25 , 26 , 27 ]. In sarcomas, this hypothesis is supported by evidence of sarcoma cells within the peritumoral “edema” that is akin to the “pseudocapsule” seen in human tumors visualized on imaging (MRI) and present at a distance from the tumor itself [ 18 ].…”