Cytoplasmic iron deposition is associated with the expression of oxidative DNA damage marker in meningiomas

Angiomatous meningiomas are rare meningioma subtypes, which are characterized by abundant, well‐formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron. In an attempt to understand its pathological significance, we assessed this unusual finding in representatives for each grade of meningiomas and immunoexpression of transferrin receptor (CD71) and the oxidative DNA damage marker, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). Iron deposition in the tumor cells was observed in 8/15 (53%) angiomatous meningioma cases, 2/6 (33%) microcystic meningiomas and 2/20 (10%) meningothelial meningiomas, which included clustered microvessels, but not in fibrous, atypical or anaplastic meningiomas (P = 0.001). Cytoplasmic CD71 expression was largely negative in angiomatous meningioma cases, but positive in meningothelial and high‐grade meningiomas, suggesting that the transferrin‐dependent iron transporter was involved in iron uptake in meningiomas. Nuclear expression of 8‐OHdG was observed in ≥50% of the tumor cells in all 15 cases of angiomatous meningioma and was associated with the presence of regressive histopathological findings, such as hyalinized vessels and cystic changes. In addition, the fraction of iron‐containing tumor cells was correlated to those expressing 8‐OHdG (P = 0.005). Our finding indicates that cytoplasmic iron deposition in tumor cells is characteristic of highly vascularized benign meningiomas and related to increased oxidative DNA damage markers.     

Metallothionein overexpression in human brain tumours

Metallothioneins (MTs) are metal binding proteins overexpressed in various human neoplasms which are associated with resistance to cytotoxic drugs. A series of 156 archival human brain tumours were investigated immunohistochemically for expression of MTs; these included 10 low-grade gliomas, 44 high-grade gliomas, 98 meningeal tumours (19 classical, 30 atypical, 38 anaplastic meningiomas, and 11 haemangiopericytomas or papillary meningiomas), and 4 other tumours. Low-grade gliomas showed heterogeneous MT expression; 32 high-grade gliomas (72.7%) showed MT expression of more than 25% of tumour cells without statistically significant differences between first operations and recurrent tumours. In 2 glioblastomas, the presence of MT was confirmed by Western blotting. The extent of MT immunoexpression showed a statistically significant inverse relationship to the degree of p53 immunoreactivity. In meningiomas, a tendency to a higher percentage of MT-expressing cells was observed from classical over atypical to anaplastic meningiomas, but these differences were not statistically significant. In conclusion, MT expression is present in a significant portion of, especially malignant, brain tumours and might be involved in their poor response to antineoplastic drugs. Received: 10 August 1995 / Revised: 15 February 1997, 14 April 1997 / Revised, accepted: 7 July 1997     

Loss of Heterozygosity at 1p, 7q, 17p, and 22q in Meningiomas

Objective

Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas.

Methods

Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively.

Results

LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas.

Conclusion

LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas.     

Topoisomerase II alpha as a reliable proliferation marker in meningiomas

The value of DNA Topoisomerase IIalpha expression as a proliferation marker in meningiomas was investigated. The correlation to MIB-1 expression and tumor grade in 85 meningiomas (60 classical, 19 atypical and 6 anaplastic) was analysed by immunohistochemistry. MIB-1 labeling indices (LI) were 1.1% (+/- 0.85) for classical meningiomas, 1.9% (+/- 1.5) for atypical meningiomas and 5.6% (+/- 4.1) for anaplastic meningiomas, differences statistically significant (p = 0.03, < 0.0001, < 0.0001). Topoisomerase IIalpha LIs were 1.4% (+/- 1.2) for classical, 3.2% (+/- 2.4) for atypical and 9.7% (+/- 6.6) for anaplastic meningiomas, differences statistically significant (p = 0.003, < 0.0001, < 0.0001). Proliferation indices based on cells staining for MIB-1 and Topoisomerase IIalpha correlated highly with one another (r= 0.906, p <0.0001). Topoisomerase IIalpha exhibited a more distinct, less variable nuclear staining pattern compared to MIB-1 expression. DNA Topoisomerase IIalpha LI represents a reliable alternative to MIB-1 as a proliferation marker in human meningiomas, especially for computer assisted assessment, where a distinct uniform staining pattern is required.     

Spinal meningiomas: age-related features

Objectives

Spinal meningiomas mainly occur in old patients, with a remarkable female prevalence. This study investigates the different features between younger and older patients in an adult population (>18 years).

Materials and methods

A surgical series of 120 adult patients operated on for spinal meningiomas at the Neurosurgical Clinic of the “Federico II” University of Naples is reviewed.In this series 117 patients with a sporadic spinal meningioma were divided in two groups: group I including 30 patients (25.6%) younger than 50 years of age, group II including 87 patients (74.4%) older than 50 years. 3 patients had a spinal meningioma and neurofibromatosis.Several parameters, including sex, predisposing factors, tumor location and growth, histology, recurrences, proliferation index Ki-67 LI, and outcome, are considered and compared in the two age groups.

Results

Group I showed an incidence of high cervical spine (C1-C4) meningiomas higher than group II (23.3% vs 3.4%, p = 0.026) and lower rate of thoracic tumors (60% vs 82.7%, p = 0.04). No significant differences of histological type and Ki-67 LI were found. Group I had 2 cases of atypical meningiomas (6.6% vs 0%, ns). Recurrences occurred in 6.6% of group I and 2.6% of group II, with no significance. In recurrent meningiomas values of Ki-67 LI were significantly higher than values in not recurrent meningiomas (p = 0.0001), whereas no difference of estrogen and progesterone receptor expression was noted.

Conclusions

Younger adult patients with spinal meningiomas show not rare occurrence of NF (9%) and significantly higher incidence of high cervical and lower incidence of thoracic localizations with respect to the older patients. On the other hand, there are not significant differences of histology, Ki-67 LI and recurrence rate, excepting for a slight difference for atypical meningiomas.     

IMMUNOHISTOCHEMICAL CHARACTERISTICS OF HAEMANGIOPERICYTIC MENINGIOMAS: COMPARISON WITH TYPICAL MENINGIOMAS, HAEMANGIOBLASTOMAS AND HAEMANGIOPERICYTOMAS FROM EXTRACRANIAL SITES

The relationship between malignant vascular meningeal tumours and typical meningiomas remains controversial, despite the need for accurate diagnostic distinction between the two, and some forms of vascular meningioma may be more closely allied to haemangioblastomas or extracranial haemangiopericytomas than to true meningiomas. In order to try to clarify the diagnostic characteristics and origins of the entity known as haemangiopericytic meningioma, 10 histologically typical cases were stained by the immunoperoxidase technique with a panel of seven antibodies. The results were compared with those obtained from typical and angiomatous meningiomas, haemangioblastomas and haemangiopericytomas from extracranial sites. Both the haemangiopericytic meningiomas and the extracranial haemangiopericytomas showed a similar staining pattern, which differed from that of the typical and angiomatous meningiomas in the strikingly focal nature of the vimentin staining and the lack of reactivity with antibodies to epithelial elements. The haemangioblastomas were less consistent in their individual staining characteristics, but had a quite different overall pattern from all the other tumour types. It is, therefore, suggested that so-called haemangiopericytic meningiomas are in fact primary haemangiopericytomas of the meninges, antigenically distinct from true meningiomas and displaying a malignant potential appropriate to haemangiopericytomas arising in any other sites.     

MIB‐1 immunolabeling: A valuable marker in prediction of benign recurring meningiomas

Histological analysis has limited value to predict biological behavior of meningiomas. We investigated the utility of cell proliferative indicator in the evaluation of histologically benign meningiomas. We selected 25 benign non‐recurrent meningiomas, 15 benign recurrent meningiomas after complete surgical resection, 30 atypical meningiomas, and 15 anaplastic meningiomas out of 384 cases studied. MIB‐1 Labeling Index was evaluated by two methods: Highest Labeling Index (HLI) and Random Labeling Index (RLI). There was no dependable histological parameter to predict recurrence among benign‐looking meningiomas. HLI had significant difference when compared with RLI in all categories. The mean MIB‐1 HLI values ± SD were 3.47 ± 2.0% for benign meningiomas, 5.08 ± 4.0% for atypical meningiomas and 11.66 ± 7.06% for anaplastic meningiomas. In comparison, the mean MIB‐1 HLI of benign non‐recurrent meningiomas were 2.66 ± 1.7% and with recurrence were 4.21 ± 2.78% (P = 0.0339). Using receiver operating characteristic, it was seen that neoplasm recurred with the MIB‐1 HLI of > 2.6 having the sensitivity of 64.6% and specificity of 68% among benign (grade I) meningiomas. MIB‐1 positive tumor cells were maximally aggregated at the periphery of excised specimen. MIB‐1 HLI, integrated with standard histopathology can provide better information about the disease biological nature in benign meningiomas.     

Diagnostic validity of the Ki-67 labeling index using the MIB-1 monoclonal antibody in the grading of meningiomas

BACKGROUND: About 10% of meningiomas behave aggressively and are graded atypical or malignant with important therapeutic and prognostic implications. Routine histological parameters are inconsistent in the assessment of their aggressive behavior. AIMS: The aim of this study was to find a threshold level of the MIB-1 labeling index (MIB-1 LI) with the highest diagnostic validity in predicting histological atypia in a meningioma. SETTING AND DESIGN: This was a retrospective study of all atypical and malignant meningiomas diagnosed at our center between January 1995 and June 2000 and which were identified from the General Pathology Registry. MATERIAL AND METHODS: These meningiomas were assessed histologically with respect to the individual criteria of atypia. They were categorized according to the WHO 2000 classification as benign, atypical and anaplastic meningiomas, WHO Grades I, II and III respectively and by immunohistochemical analysis using the MIB-1 monoclonal antibody. STATISTICAL ANALYSIS: The diagnostically useful cut-off level for the prediction of atypia was estimated by calculating the sensitivity and specificity of the MIB-1 LI at various levels and a receiver operated characteristic (ROC) analysis was performed. The correlation between the individual histological parameters was studied and the MIB-1 LI was obtained using Fisher's exact test. RESULTS: Of the 40 meningiomas studied 21 were benign, 16 atypical and 3 anaplastic. Atypical tumors had a higher MIB-1 LI than benign tumors, with diagnostic validity highest at a threshold of 7%, with a sensitivity of 0.86 and a specificity of 0.93, giving a likelihood ratio of 17. The MIB-1 LI correlated well with mitotic activity and the other individual criteria in the WHO 2000 definition of atypia in a meningioma. MIB-1 LI did not, however, correlate well with brain invasion. CONCLUSION: The MIB-1 LI has the highest validity in the diagnosis of atypia in meningiomas at a threshold level of 7%. The MIB-1 LI used in conjunction with histological features can help in making a recommendation regarding potentially aggressive behavior in meningiomas.     

Differential diagnosis of intracranial meningiomas based on magnetic resonance spectroscopy

Background and purposeTo determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial meningiomas and to assess MRS reliability in meningioma grading and discrimination from tumours of similar radiological appearance, such as lymphomas, schwannomas and haemangiopericytomas.Material and methodsAnalysis of spectra of 14 patients with meningiomas, 6 with schwannomas, 2 with lymphomas, 2 with haemangiopericytomas and 17 control spectra taken from healthy hemispheres.ResultsAll the patients with meningiomas had a high Cho signal (long TE). There were very low signals of Naa and Cr in the spectra of 10 patients. A reversed Ala doublet was seen only in 2 cases. Four patients had a negative Lac signal, whereas 3 had high Lac-Lip spectra. Twelve spectra showed high Cho signals (short TE). In one case the Cho signal was extremely low. All spectra displayed a very low Cr signal, but high Glx and Lac-Lip signals. Ala presence was found only in 3 patients. The mean Cho/Cr ratio (PRESS) was 5.97 (1.12 in normal brain, p < 0.05). Lac-Lip was present in all the meningiomas (STEAM). The Ala signal was seen only in 2 spectra with long TE and in 3 sequences of the short TE sequences. There were both β/γ-Glx and α-Glx/glutathione signals in all 14 meningiomas.ConclusionsMRS is unable to discriminate low and high grade meningiomas. The method seems to be helpful in discriminating lymphomas (absent Glx signal), schwannomas (mI signal in the short TE sequences) and haemangiopericytomas (presence of mI band) from meningiomas.     

Falx Meningiomas: Surgical Results and Lessons Learned from 68 Cases

Objective

The purpose of this study was to review the characteristics of falcine meningioma retrospectively and to identify the parameters associated with tumor recurrence.

Methods

The analysis included; age, sex, extent of resection, and radiologic and pathologic findings. Falcine meningiomas were classified by location as anterior, middle, or posterior as described for parasagittal meningiomas.

Results

Of the 795 meningioma patients treated between 1990 and 2004 at the authors'' institution, 68 patients with meningiomas arising from the falx underwent craniotomies. There were 22 male and 46 female patients (1 : 2.1). Mean age was 55 years and ranged from 14 to 77 years. Locations of falcine meningioma were; the anterior third in 33 cases, middle in 20, and posterior in 15. Mean tumor volume was 42 cc and ranged from 4 to 140 cc. In 58 of the 68 patients tumors were totally removed. Additional surgery for recurrence was performed in 6 patients over 15 years. Of these 6 patients, only two patients underwent gross total tumor resection at first operation; the other four underwent subtotal tumor resection. Based on pathologic reports, the largest tumor subtype was transitional. There were four patients with a high grade tumor-three atypical and one anaplastic meningioma. Of the 68 patients, 59 achieved a good outcome (no neurological deficit or recurrence), six had temporary complications, two suffered new permanent postoperative deficits, and the remaining one died due to severe brain swelling despite postoperative intensive care. Extent of surgical resection was found to be significantly related to tumor recurrence.

Conclusion

Falcine meningioma accounted for 8.5% of intracranial meningiomas and the transitional meningioma was the most common subtype of falcine meningioma. Gross total resection of tumor was the single most important predictor of an improved surgical outcome.     

Chromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray

Abstract

Background: Meningioma is the commonest brain tumor and many genetic abnormalities, such as the loss of chromosome 22q and the mutation of NF2, have been reported.

Methods: These classical abnormalities were detected using Southern blot, PCR, fluorescence in situ hybridization and comparative genomic hybridization, but these methods examine only very limited regions or limited mapping resolution of the tumor genome. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities simultaneously and analyses a global assessment of molecular events in meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order to detect the chromosomal aberrations and genetic abnormalities in the whole genome.

Results: This study demonstrated not only classical chromosomal aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but also new genetic characteristics of meningiomas, such as amplification of MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%) and deletion of HIRA in seven meningiomas (22.6%).

Conclusions: These results suggest that DNA microarray assay is useful in research for the genetic characters of meningiomas and understanding tumorigenesis.     

脑膜瘤血小板源生长因子及受体表达与脑膜瘤增殖活性及凋亡研究

目的 探讨血小板源生长因子（PDG－F）在脑膜瘤发生和发展中的作用。方法 采用免疫组化检测新鲜脑膜瘤组织中PDGF及其受体表达，用TUＮＥＬ法检测细胞凋亡情况，同时进行细胞增殖核抗原（PCNA）检测，结果 脑膜瘤高表达PDGF及其受体，且以表达PDGFB链及PDGF β受体为主，部分脑膜瘤表达水平很低的PDGFA链，几乎不表达PDGFa受体；非典型性脑膜瘤PDGFBB，PDGFR β蛋白表达水平及PCNA指数高于良性脑膜瘤，但同时其凋亡也增加。结论 PDGFBB／R β自分泌环可能在脑膜瘤的发生和发展过程中起着重要作用。     

Extracranially extended meningothelial meningiomas with a high MIB‐1 index: A report of two cases

Meningiomas that extend from the meninges to the extracranial tissue and result in skull osteolysis have been known to take an aggressive clinical course. Two such cases in elderly patients are reported. Case 1 is an 82‐year‐old woman who had undergone removal of the parasagittal meningioma (meningothelial meningioma with 5% of MIB‐1 index) 4 years and 6 months previously, developed recurrence of the tumor that extended to extracranial soft tissue. Biopsy obtained from the subcutaneous tissue showed an atypical meningothelial meningioma with 20% of MIB‐1 index. In case 2 an 84‐year‐old man, who developed rapidly progressing dementia and gait disturbance, the MRI study revealed an intracranial‐extraaxial right frontal tumor with an extracranial extension resulting in skull osteolysis. Pathological examination of the totally resected tumor identified meningothelial meningioma, but MIB‐1 index of the intracranial portion of the tumor was less than 0.1%, while that of the extracranial portion was approximately 15%. Although the meningiomas presently reported failed to show histological features of malignancy, the high MIB‐1 index indicated that they were rapidly growing tumors. In the present report it is considered that meningioma cells that invade the skull and extracranial tissue are biologically aggressive and require total resection, as long as the condition of the patients is feasible for surgery.     

Clinical Implications of the Mitotic Index as a Predictive Factor for Malignant Transformation of Atypical Meningiomas

ObjectiveIntracranial atypical meningiomas have a poor prognosis and high rates of recurrence. Moreover, up to one-third of the recurrences undergo high-grade transformation into malignant meningiomas. We aimed to investigate the clinical factors that can predict the propensity of malignant transformation from atypical to anaplastic meningiomas. MethodsBetween 2001 and 2018, all patients with atypical meningioma, in whom the tumors had undergone malignant transformation to anaplastic meningioma, were included. The patients’ medical records documenting the diagnosis of atypical meningioma prior to malignant transformation were reviewed to identify the predictors of transformation. The control group comprised 56 patients with atypical meningiomas who were first diagnosed between January 2017 and December 2018 and had no malignant transformation. ResultsNine patients in whom the atypical meningiomas underwent malignant transformation were included. The median time interval from diagnosis of atypical meningioma to malignant transformation was 19 months (range, 7–78). The study group showed a significant difference in heterogeneous enhancement (77.8% vs. 33.9%), bone invasion (55.6% vs. 12.5%), mitotic index (MI; 14.8±4.9 vs. 3.5±3.9), and Ki-67 index (20.7±13.9 vs. 9.5±7.1) compared with the control group. In multivariate analysis, increased MI (odds ratio, 1.436; 95% confidence interval, 1.127–1.900; p=0.004) was the only significant factor for predicting malignant transformation. ConclusionAn increased MI within atypical meningiomas might be used as a predictor of malignant transformation. Tumors at high risk for malignant transformation might require more attentive surveillance and management than other atypical meningiomas.     

The importance of microsurgery in childhood meningioma: a case report

Introduction

Although meningiomas are frequently diagnosed in adults, it is a rare (intracranial) tumor in the pediatric population, with an incidence of 0.06/100,000. The pathology and treatment of meningiomas in adulthood has been a topic of increasing investigation. So far, the treatment of pediatric meningiomas has been extrapolated from these results. The question remains, however, whether translation of adult meningioma data into the childhood population is legitimate.

Methods

We present the case of a 3-year-old girl diagnosed with an intraventricular malignant meningioma and type 2 neurofibromatosis. She was operated on multiple times to achieve complete resection and received adjuvant chemotherapy. Since, she has been stable with no neurological sequelae and/or recurrence of the meningioma.

Conclusion

Pediatric meningiomas are rare tumors and differ from their adult counterparts in various aspects. We believe that gross total resection of meningioma in the pediatric population, when possible, is the treatment of choice. In the event of a subtotal resection, repeat resection is recommended. Any adjuvant treatment with chemotherapy or radiation therapy should be carefully considered during multidisciplinary meetings.

     

Recurrent and atypical meningiomas--a multiparametric study using Ki67 labelling index,AgNOR and DNA Feulgen staining

OBJECTIVE: Histological analysis has limited value to predict the biological behavior of meningiomas. In this study, we investigated the utility of indicators of cell proliferation in the evaluation of histologically benign meningiomas. MATERIALS AND METHODS: For this purpose, 50 meningothelial meningiomas, 50 atypical meningiomas and 8 primary benign meningiomas with their recurrences were studied. For each case the Ki67 labeling index (LI), DNA ploidy and AgNOR were evaluated and the results quantitatively processed and assessed by computerized image analyzer. RESULTS: The Ki67 labelling showed a low index (11.3%) in typical meningiomas and primary meningiomas (13.6%). In contrast, it was higher in atypical (26.6%) and recurrent meningiomas (28%). Similar results were obtained for the AgNOR granule count which showed that typical and primary meningiomas had mean 1.51 - 1.49, whereas recurring meningiomas and atypical meningiomas had mean values of 1.92 and 1.98, respectively. DNA ploidy revealed in the hyperpolyploid region between 4c - 16c: 7.02% of the nuclei in primary meningiomas, 17.98% of the nuclei in recurring meningiomas and 24.63% of the nuclei in atypical meningiomas. CONCLUSION: Our results suggest that evaluation of cell proliferation using Ki67 LI, DNA ploidy and AgNOr, integrated with standard histopathology, can provide better information for a correct grading of meningiomas.     

Morphometrical analysis of nucleolin immunohistochemistry in meningiomas

Nucleolin (110 kDa) is a major nucleolar protein in eukaryotic cells and one of the nucleolar organizer region (NOR)-associated proteins. We studied immunohistochemically 32 cases of meningioma, using specific antisera against nucleolin, and analyzed various nucleolin parameters, such as the number of regions and the total area of nucleolin staining per nucleus. The mean number and area of nucleolin stainings per nucleus were compared with the histological malignancy and Ki-67/MIB-1 proliferation index; the correlation with parameters of silver-stained NOR (AgNOR) was also studied. The results showed that there were statistically significant differences in the mean number and area of nucleolin stainings per nucleus between meningiomas and other two groups, atypical and anaplastic meningiomas (P < 0.05), although there was no difference between atypical and anaplastic meningiomas. The mean number and area of nucleolin stainings per nucleus were correlated with the incidence of Ki-67 positivity and AgNOR area. In view of the technical problems inherent in AgNOR staining, immunohistochemistry for nucleolin may represent a more specific and reproducible means for NOR visualization and be a promising technique for assessing cell proliferation. Received: 4 September 1995 / Revised, accepted: 20 December 1995     

非典型性脑膜瘤与良性脑膜瘤MRI征象的对比分析

目的 对比分析非典型性脑膜瘤与良性脑膜瘤的MRI征象特点,提高对非典型性脑膜瘤的认识。方法 回顾性分析经病理证实的37例非典型性脑膜瘤与288例良性脑膜瘤的MRI征象。结果 非典型性脑膜瘤直径>6.5 cm比例、肿瘤呈分叶型比例、瘤脑界面不清晰比例、重度瘤周水肿比例、邻近骨质改变比例均明显高于良性脑膜瘤（P<0.05）。多因素Logistic回归分析显示,肿瘤较大及瘤脑界面不清晰为非典型性脑膜瘤的可能性显著增加,肿瘤大小每增加1.5 cm,非典型性脑膜瘤的概率是良性脑膜瘤的1.507倍,瘤脑界面不清晰为非典型性脑膜瘤的概率是良性脑膜瘤的2.605倍。结论 肿瘤大小及瘤脑界面对于非典型性脑膜瘤与良性脑膜瘤的鉴别诊断具有重要价值。     

Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

M. Jansen, G. Mohapatra, R. A. Betensky, C. Keohane and D. N. Louis (2012) Neuropathology and Applied Neurobiology 38, 213–219 Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression‐free survival Aims: Atypical (World Health Organization grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one‐third will recur. Post‐operative radiotherapy may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high‐resolution array comparative genomic hybridization to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumours show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression‐free survival. This study aimed to validate and extend these findings in an independent sample. Methods: Eighty‐six completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow‐up was obtained. Utilizing a dual‐colour interphase fluorescence in situ hybridization assay, 1q gain was assessed using Bacterial Artificial Chromosome probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression‐free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.