Differences in the expression of SSTR1-5 in meningiomas and its therapeutic potential

Abstract

Beyond microsurgical resection and radiation therapy, there are currently no established treatment alternatives for meningioma patients. In selected cases, peptide radio receptor therapy (PRRT) can be implemented. For this purpose, a radionuclide is bound to a substance targeting specific receptors in meningiomas. One of them is somatostatin receptor 2, which can be found in most meningiomas. However, other somatostatin receptors (SSTR) exist, but their expressions have only been described in small case series. In this study, we analyzed the expression of SSTR1, 2A, 3, 4, and 5 in a large cohort of meningiomas in order to enable further refinement of this innovative treatment option. Overall, 726 tumor samples were processed into tissue microarrays and stained for SSTR1, 2A, 3, 4, and 5 immunohistochemically. Microscopic evaluation was done with an established semiquantitative score regarding percentual quantification and staining intensity, and results were correlated with clinical data. There was a significant lower rate of SSTR1 expression in meningiomas of male patients. Older age was associated with higher expression of SSTR1, 2A, and 5 and lower scores for SSTR3 and 4. Tumors treated with radiotherapy before resection showed lower rates of SSTR1 and 5 expression, while recurrent meningiomas had lower SSTR1 scores. Tumor tissue from patients suffering from neurofibromatosis type 2 had lower expression scores for SSTR1, 2, and 5. For SSTR3 and 4, NF2 patients showed higher scores than sporadic tumors. Spinal meningiomas had higher scores for SSTR1, 4, and 5 compared tumor location of the skull base and convexity/falx. Overall, higher WHO grade was associated with lower SSTR scores. While all SSTRs were expressed, there are marked differences of SSTR expression between meningioma subgroups. This has the potential to drive the development of more selective PRRT substances with higher treatment efficacy.

Keywords: Immunohistochemistry; Meningioma; Neurofibromatosis; Peptide receptor radionuclide therapy (PRRT); Somatostatin receptor; Tissue microarray.

Fig. 1

Examples of the immunohistochemical expression of somatostatin receptor 1 (a–c), 2A (d–f), 3 (g–i), 4 (j–l), and 5 (m–o) in three meningiomas of different WHO grades. Scale bar 100 µm

Fig. 2

Distribution of the expression score of somatostatin receptors (a), 2A (b), 3 (c), 4 (d), and 5 (e). The y-axis presents the number of cases

Fig. 3

SSTR expression in different meningioma localizations (a SSTR1, b SSTR2A, c SSTR3, d SSTR4, e SSTR5); asterisk (*) presents statistically significant results

Fig. 4

SSTR expression in meningiomas of patients suffering from neurofibromatosis type 2 compared to sporadic cases (a SSTR1, b SSTR2A, c SSTR3, d SSTR4, e SSTR5); asterisk (*) presents statistically significant results

Fig. 5

SSTR expression differences among meningioma WHO grades based on the current WHO classification of central nervous system tumors (a SSTR1, b SSTR2A, c SSTR3, d SSTR4, e SSTR5); asterisk (*) presents statistically significant results