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Molecular Biologic and Scintigraphic Analyses of Somatostatin Receptor-Negative Meningiomas

Department of Dermatology, University of Cologne, Cologne; Department of Nuclear Medicine, University Hospital Eppendorf, Hamburg; and Department of Anatomy and Clinic of Nuclear Medicine, Christian-Albrechts-University, Kiel, Germany

Somatostatin receptor scintigraphy (SRS) using ¹¹¹In-octreotide has proven useful in the preoperative discrimination of expansive central nervous system lesions. Meningiomas, generally expressing human somatostatin receptor (hsst) on their surface, were detected with a sensitivity of about 100%. This finding was associated with the assumption that meningiomas lack an intact blood–brain barrier. However, this exclusion procedure became questionable when histologically proven meningiomas in which SRS was negative were reported. Therefore, the aim of this study was to discover why these meningiomas gave negative SRS results. Methods: Before surgery, 46 patients with 47 meningiomas underwent standard MRI and SRS. Thirty-four of these patients with 35 tumors were also examined by ^99mTc-diethylenetriaminepentaacetic acid (DTPA) brain scintigraphy. After surgical resection, hsst subtype 2 (hsst2) messenger RNA (mRNA) expression of 4 SRS-positive and 4 SRS-negative meningiomas was estimated semiquantitatively by reverse transcriptase polymerase chain reaction (RT-PCR). Translation of hsst2 mRNA into receptor proteins was proven immunocytochemically on the surface of 1 SRS-positive and 1 SRS-negative meningioma. Tumor specimens used for RNA extraction and RT-PCR and cultivated cells used for hsst2 immunostaining were tested for their meningioma nature by immunochemistry. Results: SRS yielded positive results in 39 meningiomas with a tumor volume of 24.1 ± 32.8 mL and negative results in 8 meningiomas with a volume of 3.9 ± 6.5 mL. ^99mTc-DTPA scintigraphy visualized 24 of 35 meningiomas. SRS was positive in all of them. In contrast, 11 meningiomas were ^99mTc-DTPA negative. In these meningiomas, SRS was negative in 5 cases (5.4 ± 8.1 mL), whereas the remaining 6 were positive (4.6 ± 4.5 mL). None of the meningiomas was ^99mTc-DTPA positive and SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA expression between SRS-positive and SRS-negative meningiomas but showed varied expression among all meningiomas regardless of SRS results. Furthermore, hsst2 proteins were visualized immunocytochemically on the surface of cultivated cells of SRS-positive and SRS-negative meningiomas. Conclusion: SRS-negative meningiomas do express hsst2; thus, in these meningiomas SRS is false-negative. Because an insufficient sensitivity was excluded, ^99mTc-DTPA scintigraphy identified a permeability barrier in SRS-negative meningiomas that explains their false-negative SRS results. SRS-negative meningiomas most likely meet the function of their tissue of origin (the meninges) to develop more-or-less intact permeability barriers.

Key Words: human somatostatin receptor • somatostatin receptor scintigraphy • ^99mTc-DTPA brain scintigraphy • reverse transcriptase polymerase chain reaction • immunohistochemistry • immunocytochemistry • meningioma • leptomeninges • blood–brain barrier • blood–tumor barrier

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