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Chromosomal aberrations in atypical and anaplastic meningiomas: A fluorescence in situ hybridization study

2015-08-04 00:01:09

Neuorlogy India: Publication of the Neurological Society of India; 04 August 2015: DOI:10.4103/0028-3886.161994


Nishanth Sadashiva, Harsh Sugur, Dwarakanath Srinivas, Vani Santosh, Sampath Somanna



Abstract


OBJECTIVE


There is significant variability in the biologic behavior of meningiomas, especially of atypical and anaplastic meningiomas, that cannot be accounted for by just histology and grade of excision. The aim of our study was to analyze deletions in regions 22q, 18p11, 1p32, and 14q32 in grade II and grade III meningiomas and their correlation with tumor grade and recurrence.

MATERIALS AND METHODS


A total of 59 samples from 50 cases of grade II and grade III meningiomas were analyzed with fluorescence in situ hybridization (FISH) technique with locus specific probes. The types of aberrations and deletions were analyzed and correlated with the tumor status.

RESULTS


There was a statistically significant increase in deletions in recurrences when compared to primary surgeries. The mean mitotic index was higher in patients with deletions. Patients with 18p deletions tended to be younger and had a significant association with sheeting. 22q deletions were associated with hypercellular tumors. 1p, 14q, and 1p14q codeletion had a significant association with mitosis ≥7.

CONCLUSION


This is a first study from India analyzing all these four sites for deletions using the FISH technique. Recurrent tumors and tumors with tendency to recur have a higher frequency of deletions. The FISH study can be used to predict the behavior of meningiomas if significant association is found. Further studies in larger sets of patients along with their clinical correlation would help in categorizing patients who have a higher risk of recurrence and help in guiding their clinical management.

INTRODUCTION


Meningiomas, originating from the arachnoid cap cells of brain and spinal cord, form 13% to 26% of all primary intracranial tumors. Grades II (atypical) and III (anaplastic) variety comprise 20% of cases, are more aggressive and are associated with increased morbidity and mortality. The extent of resection and histopathologic grading determine the recurrence and outcome. Some tumors, by virtue of their location or due to their close relation to vital structures, cannot be totally excised. Additional histopathologic, immunohistochemistry, and genetic markers may help in predicting tumor behavior and in guiding management.



Atypical meningiomas (WHO grade II) have an 8-fold increased risk of recurrence, with a statistically significant increased risk of mortality (21% at 5 years). Anaplastic meningiomas (WHO grade III) are rare (1-2%), with recurrence rates of 50-80% after surgical resection, and an average survival rate of  <2 years. In the WHO classification, the Chordoid, Clear cell, and Brain invasive meningiomas are considered grade II while the Papillary and Rhabdoid meningiomas are classified as grade III.



The 5-year recurrence rates are 5% and 41% for grade I and grade II tumors, respectively, even following Simpson's grade I resection, and this high recurrence rate is associated with an increased risk of death. Malignant meningiomas have high recurrence rates with an overall median survival of 2 years. In grade III meningiomas, surgery followed by high-dose fractionated radiotherapy are associated with a recurrence risk of 80% at 5 years. While the extent of resection and histological grade are the strongest predictors of recurrence, the significant variability in biologic behavior of these tumors cannot be completely accounted for. The molecular pathogenesis has highlighted genes that serve as newer targets to improve diagnostic and therapeutic strategies, particularly for patients with aggressive meningiomas which are resistant to the conventional forms of therapy.



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Key Words


Anaplastic meningioma | atypical meningioma | chromosomal aberration | fluorescent in situ hybridization