Abstract
Simple SummaryMeningioma diagnostics and grading are currently based on subjective histopathological criteria given by the 2016 World Health Organization (WHO) classification. However, biomarkers may provide a more objective approach to diagnostics. This study was designed to elucidate the diagnostic and prognostic value of somatostatin receptors (SSTRs) as biomarkers in meningiomas, which could help to identify patients with a higher risk of recurrence and provide more personalized treatment. We have confirmed, in a population of 162 patients, that SSTRs have diagnostic value and may aid in the differentiation between WHO grade 1 and grade 2 tumors. Furthermore, SSTR1, SSTR2 and SSTR5 were associated with higher malignancy grades. SSTR2 expression was found to be characteristic in meningiomas. To maintain objectiveness, we scoped for a digital evaluation of immunoreactivity. We aim to impact and motivate researchers to further investigations towards more objective criteria in meningioma diagnostics, which in turn will improve patient care.Meningiomas have high recurrence rates despite frequently benign histopathological appearances. Somatostatin receptors (SSTRs) may be reliable biomarkers that could identify patients with increased risk of recurrence. Even though SSTRs are previously detected in meningiomas, their associations to clinicopathological features remain unclear. The aim of this study was to investigate the diagnostic and prognostic value of SSTRs in a large series of human meningiomas with long follow-up data. Immunohistochemistry was used to measure the expression of SSTR1-SSTR5 in tissue samples from 162 patients diagnosed with intracranial meningiomas of World Health Organization (WHO) grade 1 or 2. Digital scoring and a manual staining index were applied to assess immunoreactivity. All SSTRs, except SSTR4, were upregulated in our series of meningiomas. SSTR1 (p = 0.036), SSTR2 (p = 0.036) and SSTR5 (p = 0.029) were associated with a higher malignancy grade. SSTR2 presented as the most reliable marker. Only SSTR2 was associated with time to recurrence (TTR) in univariate Cox regression analyses. Manual staining index was strongly correlated with digital scoring for all SSTRs (r > 0.65, p < 0.001). SSTRs, and especially SSTR2, are useful in the diagnostics of meningiomas, even though their prognostic value appears limited. Digital scoring is valuable to ensure reproducibility.
Highlights
Meningiomas are typically benign and slow-growing neoplasms, yet a substantial number of patients experience tumor recurrence [1,2,3,4]
The histopathological classification given by the World Health Organization (WHO) is used to design personalized treatment, but the current 2016 WHO classification for meningiomas is suboptimal due to its subjective histopathological criteria and troublesome reproducibility [2,7]
Somatostatin receptors (SSTRs) comprise a family of five (SSTR1-SSTR5) G-protein-coupled receptors that bind to the regulatory peptide somatostatin and its analogs to regulate cell growth, inhibit proliferation and angiogenesis, and promote apoptosis in both normal and neoplastic cells [11,12,13,14,15,16]
Summary
Meningiomas are typically benign and slow-growing neoplasms, yet a substantial number of patients experience tumor recurrence [1,2,3,4]. Identifying patients with increased risk for recurrence is important to provide appropriate care, especially since the current treatment options for meningiomas leave the patients vulnerable to severe complications [4,5,6]. It is necessary to find objective biomarkers that can identify patients with a higher risk for recurrence. Somatostatin receptors (SSTRs) are present in many tumors, including meningiomas [8,9,10], and may constitute diagnostic and prognostic biomarkers due to their involvement in tumorigenesis. SSTRs comprise a family of five (SSTR1-SSTR5) G-protein-coupled receptors that bind to the regulatory peptide somatostatin and its analogs to regulate cell growth, inhibit proliferation and angiogenesis, and promote apoptosis in both normal and neoplastic cells [11,12,13,14,15,16]
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