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Magnetic Resonance Imaging Characteristics Predict Epidermal Growth Factor Receptor Amplification Status in Glioblastoma

Authors' Affiliations: ¹ Neurosurgical Service; Departments of ² Neurology, ³ Neuroradiology, and ⁴ Pathology; ⁵ Stephen E. and Catherine Pappas Center for Neuro-Oncology; and ⁶ Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts

Requests for reprints: Manish Aghi, Department of Neurosurgery, Massachusetts General Hospital, Room 502, White Building, 55 Fruit Street, Boston, MA 02114. Phone: 617-840-5111; Fax: 617-726-5677; E-mail: maghi{at}partners.org.

Purpose: Two clinical-molecular glioblastoma subtypes have been described: "primary" glioblastomas arise de novo in older patients and often overexpress epidermal growth factor receptor (EGFR); "secondary" glioblastomas progress from lower-grade tumors in younger patients and commonly have TP53 mutations. EGFR overexpression correlates in experimental gliomas with increased angiogenesis, edema, and invasion. No radiographic predictors of molecular glioblastoma subtype are known.

Experimental Design: We retrospectively reviewed 75 glioblastomas, classified as TP53-mutated (n = 11), EGFR-amplified (n = 31), or neither (non-TP53/non-EGFR; n = 33). Four variables were derived from preoperative magnetic resonance imaging: (a) T2/T1, the ratio of T2-bright volume to enclosed T1-enhancing volume; (b) percentage of tumor volume that was necrosis; and (c and d) T1 and T2 border sharpness coefficients (BSC), the rates of change in grayscale intensity of adjacent 0.02-cm² voxels traversing the anterior, posterior, and lateral borders on T1-enhanced and T2 images.

Results and Conclusions: Mean T2/T1 was 4.7 for EGFR-amplified glioblastomas, greater than that of TP53-mutated glioblastomas (2.3) or non-TP53/non-EGFR glioblastomas (2.6; P < 0.00005). All four tumors with T2/T1 > 7.2 were EGFR-amplified; 0 of 15 with T2/T1 < 4.7 underwent gross total resection. The mean T2 BSC of EGFR-amplified glioblastomas was 33.7, less sharp (P < 0.0000005) than TP53-mutated (72.2) and non-TP53/non-EGFR glioblastomas (81.2). All 15 glioblastomas with T2 BSC < 30.8 were EGFR-amplified. Percentage necrosis and T1 BSC did not differ between glioblastoma subtypes. The increased T2/T1 ratio and decreased T2 BSC in EGFR-overexpressing tumors are the first radiographic distinctions described between glioblastoma molecular subtypes. These findings may reflect increased angiogenesis, edema, and/or invasion in EGFR-overexpressing tumors.

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