Osteopontin expressions correlate with WHO grades and predict recurrence in meningiomas

Recurrence of meningiomas is a major prognostic issue. Although World Health Organization (WHO) histopathological grading correlates strongly with recurrence, it has some limitations, and predicting the biological behavior of grade I meningiomas is particularly difficult. Osteopontin (OPN) is a protein known to be involved in tumor progression. The purpose of this study is to determine expression of OPN in meningiomas and to investigate its correlation with WHO grades and tumor recurrence. Immunohistochemical (IHC) evaluation of expression of OPN was performed by two different methods to ensure reliability. OPN IHC and Allred scores were calculated on the basis of intensity and extent of staining. Both scores were in agreement and correlated significantly with meningioma grade and Ki-67 index. OPN scores were also significantly correlated with recurrence of WHO grade I meningiomas. Cut-off values for OPN IHC and OPN Allred scores between non-recurrent and recurrent grade I meningiomas were calculated as 70 and 5.5 respectively. We concluded that OPN is a valuable marker for grading meningiomas and for predicting the recurrence in WHO grade I tumors.     

Karyopherin a2 and chromosome region maintenance protein 1 expression in meningiomas: novel biomarkers for recurrence and malignant progression

The karyopherin protein family comprises importins and exportins which are nucleocytoplasmic shuttling receptors. Increased levels of karyopherin a2 and chromosome region maintenance protein 1 correlate with a higher WHO grade and a poorer prognosis in patients with infiltrative astrocytomas. The aim of this study was to evaluate representative members of importins and exportins (i.e. karyopherin a2 and chromosome region maintenance protein 1) as novel biomarkers for meningiomas of WHO grades I–III. We semiquantitatively analyzed nuclear expression of karyopherin a2, chromosome region maintenance protein 1 and the MIB1 labeling index using immunohistochemistry in 108 primary (44 meningiomas WHO grade I, 48 meningiomas WHO grade II, 16 meningiomas WHO grade III) and 13 recurrent meningiomas. Statistical analysis was performed using standard techniques. Karyopherin a2 (p < 0.001) and chromosome region maintenance protein 1 (p = 0.002) expression correlated significantly with the histological grade. Karyopherin a2 expression correlated with proliferative activity as assessed by the MIB1 index (p < 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) when compared to primary growths. Multivariate analysis of the overall series as well as of patients with atypical meningiomas identified higher karyopherin a2 (≥5 vs. <5 %) and chromosome region maintenance protein 1 (≥60 vs. 60 %) expression as independent predictors of tumor recurrence. Karyopherin a2 and chromosome region maintenance protein 1 expression may have potential as novel biomarkers for meningiomas.     

SPARC: a potential diagnostic marker of invasive meningiomas.

SPARC, a secreted, extracellular matrix-associated protein implicated in the modulation of cell adhesion and migration, was evaluated as a marker for invasive meningiomas. Although the majority of meningiomas are clinically and morphologically benign, approximately 10% progress into atypical and malignant tumors, according to the standard criteria. However, a subset of meningiomas presents as histomorphologically benign tumors (WHO grade I), but they are clinically invasive. It has been suggested that these tumors should be classified as malignant, and that the patients may require adjuvant therapy and closer follow up. Unfortunately, a significant number of these tumors may not be recognized because the surgical specimen used to assess the grade of a tumor lacks the infiltrative interface with the brain, which is currently necessary to determine its invasive character. Therefore, a marker of heightened invasiveness would greatly facilitate the identification of this subset of patients. In this study, the immunohistochemical expression of SPARC in benign, noninvasive primary meningiomas was compared with its expression in invasive, aggressive, primary and recurrent meningiomas. SPARC was not expressed in the 9 benign, noninvasive tumors, but was highly expressed in the 20 invasive tumors, regardless of the grade. The findings suggest that SPARC is a potential diagnostic marker of invasive meningiomas and is capable of distinguishing the histomorphologically benign noninvasive from the histomorphologically benign but invasive meningiomas, in the absence of the infiltrative interface.     

Tumor grade-related <Emphasis Type="Italic">NDRG2</Emphasis> gene expression in primary and recurrent intracranial meningiomas

Approximately 30% of all primary CNS tumors are meningiomas. Depending on histological type, meningiomas can recur as follows: benign—with five-year recurrence of 5%, atypical—recurrence approximately 40%, and anaplastic with recurrence of 50–80%. In an attempt to understand the molecular mechanism of meningioma recurrence we investigated the N-Myc downstream-regulated gene 2 (NDRG2), which has recently been described as important in suppressing cellular carcinogenesis in different types of cancer. The objective of the study was to investigate NDRG2 gene expression at the mRNA level in primary and recurrent meningiomas as a potential marker of tumor aggressiveness, malignancy, and recurrence. Primary and recurrent meningiomas of WHO grades I, II, and III from 35 patients operated on between 2005 and 2008 year at the Department of Neurosurgery of Kaunas Medical University Hospital (Lithuania) were studied. Using the qRT-PCR method we measured NDRG2 gene expression at the mRNA level in primary (n = 24) and recurrent (n = 11) meningiomas. Statistically significant differences in NDRG2 gene expression level were observed between primary and recurrent meningioma groups (P < 0.05) and between benign (WHO grade I) and atypical (WHO grade II) meningiomas (P < 0.05). No statistically significant differences were observed (P > 0.05) among histological subtypes of benign (WHO grade I) meningiomas: fibrous, meningothelial, and transitional. In accordance with our results, reduction of NDRG2 gene expression at the mRNA level could help to explain malignant progression and predisposition to recurrence in meningiomas.     

Fatty acid synthase is a predictive marker for aggressiveness in meningiomas

Meningiomas are the most frequent intracranial tumors. Although most are benign WHO grade I tumors, grade II and III tumors are aggressive and survival is poor. Treatment options for grade II and III meningiomas are limited, and molecular targets are few. The re-programming of metabolic pathways including glycolysis, lipogenesis, and nucleotide synthesis is a hallmark of the physiological changes in cancer cells. Because fatty acid synthase (FAS), the enzyme responsible for the de-novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers, we investigated its involvement in meningiomas. We subjected 92 paraffin-embedded samples from 57 patients with grade I, 18 with grade II and III, and six with radiation-induced tumors to immunohistochemical study of FAS. Whereas its expression was increased in grade II and III meningiomas (62.9 %) compared with grade I tumors (29.8 %) (chi-squared test: p < 0.001), FAS was expressed in grade I tumors with a high MIB-1 index and infiltration into surrounded tissues. All radiation-induced meningiomas expressed FAS and its expression was positively correlated with the MIB-1 index (p < 0.005). Our findings suggest that increased FAS expression reflects the aggressiveness of meningiomas and that it may be a novel therapeutic target for treatment of unresectable or malignant tumors.     

Expression of the hypoxia marker carbonic anhydrase 9 is associated with anaplastic phenotypes in meningiomas.

PURPOSE: Hypoxia in the tumor microenvironment triggers a variety of genetic and adaptive responses that regulate tumor growth. Tumor hypoxia is often associated with more malignant phenotypes, resistance to therapy, and poor survival. The purpose of this study was to evaluate the prevalence of hypoxia in meningiomas using the endogenous hypoxia marker carbonic anhydrase 9 (CA9) and to relate the expression of CA9 to tumor vascularity, histopathologic grade, and clinical variables, such as recurrent tumor status. EXPERIMENTAL DESIGN: Expression of CA9 and CD34, an endothelial cell marker, was examined in serial paraffin-embedded sections by immunohistochemistry in 25 grade 1, 17 grade 2, and 20 grade 3 meningiomas. Areas of immunoreactivity were semiquantitatively scored and correlated to clinical variables using Statistical Analysis System statistical software. RESULTS: Approximately 50% (29 of 62) of all meningiomas contained regions of hypoxia as judged by expression of CA9, and this expression was significantly associated with higher-grade histology (P = 0.001). In contrast, vascularity, as assessed by the percentage of vascular hotspots, was inversely associated with tumor grade (P = 0.023) and was not associated with CA9 expression. Among lower-grade meningiomas, CA9 expression tended to be more common in recurrent tumors. CONCLUSIONS: Tumor hypoxia is an endogenous feature of meningiomas, and therapeutic regimens should include strategies to target the subpopulation of hypoxic as well as the normoxic cells within the tumor. Hypoxia in meningiomas is associated with an aggressive phenotype. Further studies to define the contribution of hypoxia to meningioma pathophysiology are warranted.     

Fatty acid synthase as a novel target for meningioma therapy

High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.     

Somatostatin Receptor Theranostics for Refractory Meningiomas

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas (n = 29); 57.1% for WHO grade II (n = 21); and 0 % for WHO grade III (n = 12). For all grades (n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.     

Polyamine metabolism in gliomas

Summary Biosynthesis of the polyamines putrescine, spermidine, and spermine has been found to be activated in tissues with cellular proliferation. In the present study we have investigated polyamine levels and the activity of the first rate-limiting enzyme ornithine decarboxylase (ODC) in tumour samples obtained during operation of 202 patients with gliomas. Biochemical data were closely related to the grading of malignancy and to the morphological characteristics of each sample. Mean ODC activity was significantly higher in all gliomas as compared to peritumoural non-neoplastic brain. Furthermore, it was significantly higher (p 0.001) in anaplastic gliomas who grade III and IV (9.0 ± 9.6 nmol/g/h) than in gliomas WHO grade I and II (3.3 ± 4.2 nmol/g/h). Highest enzyme activity (58.5 nmol/g/h) was found in solid and vital parts of malignant tumours, whereas predominantly necrotic areas exhibited low ODC activity (< 1 nmol/g/h). Thus, intra- and interindividual variability of ODC activity corresponded well to histomorphological heterogeneity in high-grade gliomas. Putrescine levels also increased with rising grade of malignancy, whereas spermidine and spermine levels did not correlate with the histological grading. In conclusion, high ODC activity represents a biochemical marker of malignancy in gliomas, but low values do not prove benignity. The present study reinforces the need of further and more extensive tumour sampling closely related to follow-up investigations in the heterogeneous group of gliomas.     

Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4–8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.     

EGF signalling and rapamycin-mediated mTOR inhibition in glioblastoma multiforme evaluated by phospho-specific flow cytometry

Various degrees of peritumoral brain edema (PTBE) are observed in patients with intracranial meningiomas. Factors affecting the occurrence of PTBE in intracranial meningioma were investigated. PTBE was investigated retrospectively for 110 patients with primary intracranial meningiomas. Predictive factors related to PTBE were analyzed, for example patient age, sex, magnetic resonance imaging features (contrast enhancement, tumor shape, tumor location, tumor volume), angiographical features (tumor stain, pial–cortical arterial supply, venous obstruction), and histopathological features (histological subtypes, mindbomb homolog 1 labeling index (MIB1-LI)). Histological subtypes were classified into World Health Organization (WHO) grade I common type (meningothelial, transitional, fibrous), grade I uncommon type, and grade II and III types. The extent of PTBE was assessed by calculation of the edema index (EI). PTBE was present in 53 cases (48 %). Male sex, heterogeneous enhancement, superficial location, tumor volume (≥10 cm³), remarkable tumor stain, pial supply, venous obstruction, malignant pathology, and MIB1-LI ≥4 % were correlated with PTBE in univariate analysis. Pial supply and remarkable tumor stain were correlated with PTBE in multivariate analysis. WHO grade I uncommon type had obviously higher EI than WHO grade I common type, and WHO grade II and III types (P < 0.001). Seven cases with prominently high EI (EI ≥10) were all WHO grade I uncommon type, including angiomatous, microcystic, secretory, and lymphoplasmacyte-rich meningioma. Prominently extensive PTBE might indicate the presence of WHO grade I uncommon type meningioma.     

Histopathological parameters with Ki-67 and bcl-2 in the prognosis of meningiomas according to WHO 2000 classification

AIMS AND BACKGROUND: Meningiomas are classified following the WHO system of 2000 into three grades, benign (grade I), atypical (grade II), and anaplastic (grade III). We investigated the relation between tumor grade and Ki-67 and bcl-2. METHODS: In the present study, 246 cases of meningioma were reclassified according to the WHO 2000 system. The relationship between tumor grade and morphological parameters like pattern, mitotic index, cellularity, pleomorphism, nucleoli, small cell population with high nucleus/cytoplasmic ratio, necrosis and brain invasion was examined. Follow-up data were available for only 80 patients. RESULTS: A correlation was found between all morphologic parameters except for brain invasion. These parameters were related to a poor prognosis. There was no statistically significant difference in the prognosis between WHO grade I and grade II, whereas these two grades collectively exhibited significantly better survival than WHO grade III. Immunohistochemical staining for Ki-67 and bcl-2 was performed, and correlations between their expressions and other clinicopathological findings were investigated. Ki-67 and bcl-2 expression was correlated with tumor grade, and the higher the tumor grade, the higher the Ki-67 and bcl-2 expression. In conclusion, tumor grade appeared to be the most important parameter for a prognosis of meningiomas. CONCLUSIONS: Ki-67 and bcl-2 expression might participate in carcinogenesis and when used with the grading system could provide additional benefit in assessing the biological behavior of the tumor.     

Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01–08)

Platelet-derived growth factor (PDGF) and its receptors (PDGFR) are frequently coexpressed in meningiomas, potentially contributing to their pathogenesis. The North American Brain Tumor Consortium conducted a phase II study to evaluate the therapeutic potential of imatinib mesylate (Gleevec), a PDGFR inhibitor, in patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical (WHO grade II) and malignant (WHO grade III) meningiomas. The primary end point was 6-month progression-free survival (6M-PFS). Patients requiring enzyme-inducing antiepileptic drugs were ineligible. Patients received imatinib at a dose of 600 mg/day for the first 4-week cycle and then gradually increased to 800 mg/day for subsequent cycles, if there were no unacceptable toxicities. Plasma concentrations of imatinib and its active metabolite, {"type":"entrez-protein","attrs":{"text":"CGP74588","term_id":"875877231","term_text":"CGP74588"}}CGP74588, were assessed. Twenty-three heavily pre-treated patients were enrolled into the study (13 benign, 5 atypical, and 5 malignant meningiomas), of whom 22 were eligible. The study was closed prematurely due to slow accrual. Tissue was available only from a minority of patients, but in these specimens there was uniform distribution of PDGFR, the drug target. Imatinib was generally well tolerated. Of 19 patients evaluable for response, 10 progressed at the first scan, and 9 were stable. There were no complete or partial responses. Overall median PFS was 2 months (range, 0.7–34 months); 6M-PFS was 29.4%. For benign meningiomas, median PFS was 3 months (range, 1.1–34 months); 6M-PFS was 45%. For atypical and malignant meningiomas, median PFS was 2 months (range, 0.7–3.7 months); 6M-PFS was 0%. Cycle 1 trough concentrations of imatinib and {"type":"entrez-protein","attrs":{"text":"CGP74588","term_id":"875877231","term_text":"CGP74588"}}CGP74588 were 2,129 ± 1,600 ng/ml and 517 ± 326 ng/ml, respectively. Single-agent imatinib was well tolerated but had no significant activity in recurrent meningiomas. Trough plasma concentrations of imatinib exceeded those associated with imatinib activity in chronic myelogenous leukemia.     

建立人脑胶质瘤恶性进展相关基因表达谱

目的：建立人脑胶质瘤恶性进展相关基因表达谱。方法：用微阵列技术对同一胶质瘤患者初发(WHOⅡ级)、复发(WHOⅢ级)和再发(WHOⅣ级)的3次手术标本中基因差异表达情况进行检测,并以第3次手术时切取的正常脑组织作为对照。结果：全组共获取16363个数据。3份肿瘤标本中,表达差异≥3倍的基因共197条。将含正常脑组织在内的4份标本进行两两比较,表达差异≥3倍的基因共489条(上调193,下调296)。再将已知功能的109条基因按出现频率排列,由高到低依次为发育、代谢、分化、信号传导、DNA结合转录、细胞受体、免疫、DNA合成修复重组、离子通道运输、蛋白翻译合成、细胞骨架运动、应激、原癌和抑癌、细胞凋亡、细胞周期相关基因。结论：从处于恶性进展不同阶段的人脑胶质瘤手术标本中发现了197条表达差异≥3倍的基因,同时经生物信息学分析,发现17条候选新基因,它们在胶质瘤发生与发展的分子机制中起重要作用。     

Pretreatment dynamic contrast-enhanced MRI biomarkers correlate with progression-free survival in primary central nervous system lymphoma

Recurrence rates of meningiomas have been widely reported in the literature, but it remains challenging for clinicians to predict recurrence rate depending on treatment, patient demographics and tumor characteristics. To address these needs, we performed a systematic analysis of the literature to determine the recurrence rate ranges of meningiomas following surgery or radiation. Our search yielded 13 studies that met all criteria for inclusion, allowing us to include 1539 patients in the assessment. Recurrence rates ranged from 0.00 to 2.36 per 100-person-years for WHO grade I meningiomas; and from 7.35 to 11.46 per 100-person-years for WHO grade II meningiomas. Our findings suggest that (1) reported recurrence rates are variable and complicated by the heterogeneity of study populations; (2) as expected, WHO grade II meningiomas generally have a higher recurrence rate than WHO grade I, when controlling for time of diagnosis (by employing person-years); and (3) there is a need for more rigorous reporting of recurrence rates, WHO grade, and Simpson grading for individual patients in order to determine a robust mean of recurrence across WHO grades.     

Comparative proteomic profiles of meningioma subtypes

Meningiomas are classified into three groups (benign, atypical, and anaplastic) based on morphologic characteristics. Atypical meningiomas, which are WHO grade 2 tumors, and anaplastic meningiomas, which are WHO grade 3 tumors, exhibit an increased risk of recurrence and premature death compared with benign WHO grade 1 tumors. Although atypical and anaplastic meningiomas account for <10% of all of meningiomas, it can be difficult to distinguish them from benign meningiomas by morphologic criteria alone. We used selective tissue microdissection to examine 24 human meningiomas and did two-dimensional gel electrophoresis to determine protein expression patterns. Proteins expressed differentially by meningiomas of each WHO grade were identified and sequenced. Proteomic analysis revealed protein expression patterns unique to WHO grade 1, 2, and 3 meningiomas and identified 24 proteins that distinguish each subtype. Fifteen proteins showed significant changes in expression level between benign and atypical meningiomas, whereas nine distinguished atypical from anaplastic meningiomas. Differential protein expression was confirmed by Western blotting and immunohistochemistry. We established differential proteomic profiles that characterize and distinguish meningiomas of increasing grades. The proteins and proteomic profiles enhance understanding of the pathogenesis of meningiomas and have implications for diagnosis, prognosis, and treatment.     

The Expression of Survivin and Ki-67 in Meningiomas: Correlation with Grade and Clinical Outcome

Identification of proteins involving in the control of proliferation in normal cells may lead to a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity may help determine the tumor grade, recurrence and malignancy. Forty meningiomas of various histological grade, diagnosed in Baskent University and Cukurova University Medical Faculty, Departments of Pathology, were graded according to WHO grading system and survivin and Ki-67 monoclonal antibodies were administered by immunohistochemical method. Findings were analyzed with statistical methods; distribution of survivin expression and Ki-67 LI values were determined for different grade meningiomas. The correlation between increasing grades of meningiomas, particularly between grades I and III, survivin and Ki-67 LI values was statistically significant. In addition, we have found a positive correlation between clinical outcome, survivin and Ki-67 LI. For over expression of survivin in some of the grade I meningiomas and no or mild expression in some of the grades II and III meningiomas, however, it has been suggested that apoptosis inhibited by survivin is not the only factor responsible for progression of meningiomas.     

Expressions of Progesterone Receptor of Orbital Meningiomas in Indonesia

Objective: Visual disturbances that can heal after a complete resection of orbital meningiomas are only about 2.9%. Grading and expression of the progesterone receptor (PR) in orbital meningiomas, according to World Health Organization (WHO) is a useful predictive value of recurrence in the treatment management of orbital meningiomas. This study aims to determine the relationship of PR expression on the grading of orbital meningiomas as tumour prognostic factors. Methods: This cross-sectional observational analysis observed 44 orbital meningioma in Cicendo Eye Hospital Bandung and Hasan Sadikin Hospital between 2017-2020. We performed of mRNA PR with RT-qPCR technique and calculation with the 2∆∆Ct formula. Statistical analysis used the Kruskal-Wallis Test, followed by the Mann-Whitney post hoc test with p<0.005. Results: Relative expression of mRNA PR in meningioma orbita grade I to grade III decreased significantly the expression of relative mRNA PR at grade I, II, III of 21.69±44.35, 20.39±26.30 and 1.25±0.85, with Kruskal-Wallis test, p =0.007. Mann Whitney’s test results showed relative mRNA PR expression between grades I and II not different (p = 0.055), relative expression mRNA PR between grades I and III differed significantly (p = 0.024), and relative expression mRNA PR between grades I and III was not different (p = 0.638). Conclusion: mRNA PR expression is viable for prognostic value, predicting recurrence and implementing more effective management of subsequent therapy, it must be combined with other markers to determine the nature of the orbital meningioma.