Molecular biologic and scintigraphic analyses of somatostatin receptor-negative meningiomas

Somatostatin receptor scintigraphy (SRS) using (111)ln-octreoticle has prov en useful in the preoperative discrimination of expansive central nervous s ystem lesions. Meningiomas, generally expressing human somatostatin recepto r (hsst) on their surface, were detected with a sensitivity of about 100%. This finding was associated with the assumption that meningiomas lack an in tact blood-brain barrier. However, this exclusion procedure became question able when histologically proven meningiomas in which SRS was negative were reported. Therefore, the aim of this study was to discover why these mening iomas gave negative SRS results. Methods: Before surgery, 46 patients with 47 meningiomas underwent standard MRI and SRS. Thirty-four of these patient s with 35 tumors were also examined by Tc-99m-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 poly merase chain reaction (RT-PCR). Translation of hsst2 mRNA into receptor pro teins was proven immunocytochemically on the surface of 1 SRS-positive and I SRS-negative meningioma. Tumor specimens used for RNA extraction and RT-P CR and cultivated cells used for hsst2 immunostaining were tested for their meningioma nature by immunochemistry. Results: SRS yielded positive result s in 39 meningiomas with a tumor volume of 24.1 +/- 32.8 mL and negative re sults in 8 meningiomas with a volume of 3.9 +/- 6.5 mL. Tc-99m-DTPA scintig raphy visualized 24 of 35 meningiomas. SRS was positive in all of them. In contrast, 11 meningiomas were Tc-99m-DTPA negative. In these meningiomas, S RS was negative in 5 cases (5.4 +/- 8.1 mL), whereas the remaining 6 were p ositive (4.6 +/- 4.5 mL). None of the meningiomas was 99mTc-DTPA positive a nd SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA ex pression between SRS-positive and SRS-negative meningiomas but showed varie d expression among all meningiomas regardless of SRS results. Furthermore, hsst2 proteins were visualized immunocytochemically on the surface of culti vated cells of SRS-positive and SRS-negative meningiomas. Conclusion: SRS-n egative meningiomas do express hsst2; thus, in these meningiomas SRS is fal se-negative. Because an insufficient sensitivity was excluded, 99mTc-DTPA s cintigraphy identified a permeability barrier in SRS-negative meningiomas t hat explains their false-negative SRS results. SRS-negative meningiomas mos t likely meet the function of their tissue of origin (the meninges) to deve lop more-or-less intact permeability barriers.