Immunocytochemical analysis of glucose transporter protein‐1 (GLUT‐1) in typical, brain invasive, atypical and anaplastic meningioma

Abstract

Glucose transporter-1 (GLUT-1) is one of the major isoforms of the family of glucose transporter proteins that facilitates the import of glucose in human cells to fuel anaerobic metabolism. The present study was meant to determine the extent of the anaerobic/hypoxic state of the intratumoral microenvironment by staining for GLUT-1 in intracranial non-embolized typical (WHO grade I; n = 40), brain invasive and atypical (each WHO grade II; n = 38) and anaplastic meningiomas (WHO grade III, n = 6). In addition, GLUT-1 staining levels were compared with the various histological criteria used for diagnosing WHO grade II and III meningiomas, namely, brain invasion, increased mitotic activity and atypical cytoarchitectural change, defined by the presence of at least three out of hypercellularity, sheet-like growth, prominent nucleoli, small cell change and "spontaneous" necrosis. The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS = 1-4) and to be consistently strong in WHO grade III meningiomas (IRS = 6-12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS = 1-9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS = 0-4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in angiomatous WHO grade I meningioma. (4) "Spontaneous" necrosis and small cell change typically occurred away from the intratumoral capillary network embedded within the pattern of GLUT-1 staining. Taken together, GLUT-1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with "spontaneous" necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma.

Serum lactate as a potential biomarker of non-glial brain tumors

“…As per the tumor grading, atypical meningiomas are benign tumors with malignant potential. The Warburg effect is described in higher grade meningiomas [5], which explains the elevated lactate in atypical meningioma patients. To date, there has been no study to examine the Warburg effect in benign Grade I meningiomas.…”

Expression of GLUT3 and HIF-1α in Meningiomas of Various Grades Correlated with Peritumoral Brain Edema

“…Nes et al [ 15 ] have found that GLUT1 expression is spatially separated from the intratumoral vascular network, indicating that this atypical histologic alteration represents a cellular response to diffusion-limited hypoxia. GLUT3 is the most abundant glucose transporter in the brain except for GLUT1.…”

“…A zone in each section was identified under a low magnification microscope, wherein there was a uniform distribution of cells, and a high proportion of positive cells was observed under high power (200×). Serious local hypoxic conditions may eventually lead to necrosis; therefore, to determine the tumor hypoxia levels for statistical analysis, an estimate of the area of tumor necrosis was added to the estimate of the degree of GLUT3 staining [ 15 ].…”

Correlation of pretreatment 18F-FDG uptake with clinicopathological factors and prognosis in patients with newly diagnosed diffuse large B-cell lymphoma

“…According to the percentage of Ki-67-positive cells, patients were divided into a high Ki-67 expression group (% expression> 50%) and a low Ki-67 expression group (% expression≤50%). The semiquantitative immunoreactive score (IRS) method was used to calculate the expressions of the Glut-1 and Glut-3 proteins 21 , 22 . Staining intensity was scored as follows: no staining, 0 points; weak staining, 1 point; moderate staining, 2 points; and strong staining, 3 points.…”