. The end of follow-up was 1 January, 2009. Median follow-up time was 11 years.
Additional tissue samples were collected to establish the SSTRs expression in adjacent meninges and the following differential diagnoses: neurofibroma, schwannoma, solitary fibrous tumor/hemangiopericytoma and hemangioblastoma. Two formalin-fixed, paraffinembedded tissue specimens of each differential diagnosis and ten adjacent meninges to tumor tissue were obtained.

Immunohistochemistry
Paraffin sections of 4 micrometers were dried overnight at 37 • C and then for one hour at 60 • C before deparaffinization and rehydration. Heat induced epitope retrieval (HIER) was performed in target retrieval solution (TRS) pH6 for 20 min at 97 • C and then cooled to 65 • C, conducted by PT Link (DAKO Denmark A/S, Produktionsvej 42 DK-2600 Glostrup, Denmark). DAKO Autostainer Plus was used for immunodetection. After incubation of primary antibodies, sections were treated for 10 min in Dako REAL Peroxidase Blocking Solution (S2023) to prevent endogenous peroxidase activity. Secondary antibodies were incubated for 30 min (HRP Rabbit/Mouse EnVision-Polymer, Dako REAL Envision Detection System K 5007). DAB+ Chromogen (Dako REAL Envision Detection System) was utilized for 10 min before conducting hematoxylin counterstain. Lastly, sections were dehydrated and coverslips applied. Positive controls of duodenum, stomach, pancreas and pituitary gland were treated in the same manner as tumor samples. The primary antibodies were omitted for negative controls. Details on antibodies are listed in Table 1. TMA cores with <50% remaining tissue were excluded.

Manual Scoring of Immunohistochemistry
Each tumor was given a staining index (SI) by an experienced neuropathologist (S.H.T.) as part of the manual evaluation of immunohistochemistry (IHC). SI was defined as the product of percentage of positive cells and staining intensity. Percentage of positive cells was scored as <10% (1), 10-50% (2) or >50% (3), while intensity was scored as negative (0), weak (1), moderate (2) or strong (3) [27]. One collective SI was estimated for all three TMA cores from each patient.
The immunoreactivity of differential diagnoses and meninges was manually assessed and quantified as positive or negative.

Image Acquisition and Digital Evaluation of SSTRs Expression
A digital evaluation of SSTRs expression was conducted as suggested by Varghese et al. [28] with adjustments. Each TMA core had a diameter of 1000 µm and were constructed from areas with only tumor tissue and without hemorrhage or necrosis. All TMA cores were scanned using Olympus VS120S5 with a ×20 objective lens and the resulting images were processed in ImageJ, version 1.53c. Color deconvolution is a technique to transform the ordinary color channels of an image (such as red, green, and blue) to channels representing specified colors [29]. In ImageJ, color deconvolution was applied with "H DAB" as vector so that a new image was generated where the pixel intensity reflects the intensity of H DAB in the corresponding pixel in the original image. Next, a histogram of pixels per intensity was created for each image (Supplementary File S1). The intensity of each pixel was measured on a scale from 0 (darkest shade of color) to 255 (lightest shade of color). The total number of pixels per sample was 24,304,900. To exclude background stain from the digital analysis, a threshold was preselected for each SSTR, where pixels with intensity values over the selected threshold predominantly constituted background stain and were omitted from the calculation of digital score (DS) and subsequent analysis. The thresholds were based on manual evaluation of five TMA cores from different patients and were as follows: 220 for SSTR1, 219 for SSTR2, 222 for SSTR3, 211 for SSTR4, and 221 for SSTR5. The remaining pixels were divided into four zones based on intensity, and each zone was assigned one of the following scores [28]: highly positive (intensities < 61, score 4), positive (intensities 61-120, score 3), low positive (intensities 121-180, score 2), and negative (inten-sities >180, score 1). A digital score (DS) was calculated as the sum of zone scores weighted by the proportion of pixels in the corresponding zone, as Formula (1): DS = 4·n Highly positive + 3·n Positive + 2·n Low positive + n Negative /N Total (1) where N Total is the total number of pixels and n the number of pixels in the corresponding zone [28]. Thus, DS ranges from 1 (negative pixels only) to 4 (highly positive pixels only). A single score was sustained for the three TMA cores of each patient. DSs were calculated in RStudio, version 4.0.2 (Supplementary File S2).

Statistical Analysis
Spearman's rank-order correlation was applied to determine the correlation between DS and SI of each SSTR. The DS are continuous variables and may provide a more objective measure than SI. Hence, only the DS were used for further statistical analyses.
Mann-Whitney U test was used to compare the expression of SSTRs to the following dichotomic histological features: (1) 2016 WHO grade, (2) necrosis (yes/no), (3) hypercellularity (yes/no), (4) sheeting (yes/no), (5) macronuclei (yes/no), (6) small cells (yes/no) and (7) psammoma bodies (yes/no). Kruskal-Wallis test was applied to variables with more than two groups (tumor subtype), and if significant, followed by Dunn's test and Holm-Bonferroni adjustment to preserve the familywise error rate. Tumor subtypes included meningothelial, fibrous, transitional and atypical tumors, as subtypes with only a single patient were excluded from the analysis.
Time to recurrence (TTR) and overall survival (OS) were used as endpoints for Cox regression analyses, where the digital SSTR scores were applied as continuous covariates. TTR was defined as time to recurrence or disease-related death [30].
Statistical analyses were conducted in IBM SPSS Statistics for Windows, Version 26.0. A p-value of <0.05 was considered significant.

Patients
Among the 162 patients included, the median age at operation was 60 years (range: 25-86 years) and 73.5% (119 patients) were female ( Table 2). In compliance with the 2016 WHO classification, 109 patients (67.3%) were diagnosed with grade 1 and 53 patients (32.7%) with grade 2. Most patients (84%) underwent a gross total resection (Simpson grade I-III) and were scored to WHO performance status 1 (68.7%). At follow-up, 41 patients had suffered from recurrence.

Immunohistochemical Expression of SSTRs in Meningiomas
The expression of SSTRs was assessed both manually and digitally (Table 3). Using manual staining index (SI), SSTR1 and SSTR2 presented with a median SI of 9, while SSTR3 and SSTR5 had a median SI of 6. SSTR4 had the weakest immunoreactivity (median SI = 0). With digital scoring (DS), SSTR1 (median DS = 2.72), SSTR2 (median DS = 2.24) and SSTR3 (median DS = 2.09) had the strongest immunoreactivity, while SSTR4 (median DS = 1.14) and SSTR5 (median DS = 1.51) had a weaker immunoreactivity. Table 3. Digital scoring and staining index of immunohistochemical expression of SSTRs in human meningiomas. The digital score goes from 1 to 4, whereas the staining index goes from 0 to 9. The expression pattern varied between the SSTRs (Figures 1 and 2). SSTR1 and -2 had strong immunoreactivity, while SSTR3 and -5 exhibited a more moderate expression. In contrast, SSTR4 had sparse immunoreactivity. Cytoplasmatic immunoreactivity was observed for all SSTRs, while additional nuclear and membranous immunoreactivity was reported in some tumors for SSTR1 and -3. Also, SSTR4 occasionally expressed nuclear immunoreactivity. Regarding SSTR5, both nuclear and cytoplasmatic immunoreactivity were detected in all positive meningiomas. Fibroblasts were used as an internal negative control for all SSTRs. One tumor was excluded from further analysis due to lack of tissue after preparation.

Immunohistochemical Expression of SSTRs in Meningiomas
The expression of SSTRs was assessed both manually and digitally (Table 3). Using manual staining index (SI), SSTR1 and SSTR2 presented with a median SI of 9, while SSTR3 and SSTR5 had a median SI of 6. SSTR4 had the weakest immunoreactivity (median SI = 0). With digital scoring (DS), SSTR1 (median DS = 2.72), SSTR2 (median DS = 2.24) and SSTR3 (median DS = 2.09) had the strongest immunoreactivity, while SSTR4 (median DS = 1.14) and SSTR5 (median DS = 1.51) had a weaker immunoreactivity. Table 3. Digital scoring and staining index of immunohistochemical expression of SSTRs in human meningiomas. The digital score goes from 1 to 4, whereas the staining index goes from 0 to 9. The expression pattern varied between the SSTRs (Figures 1 and 2). SSTR1 and -2 had strong immunoreactivity, while SSTR3 and -5 exhibited a