Clinicopathological variables, immunophenotype, chromosome 1p36 loss and tumour recurrence of 247 meningiomas grade I and II

Abstract

The WHO grading scheme distinguishesbenign (grade I), atypical (grade II) and anaplastic(grade III) meningiomas. Both atypical and anaplasticmeningiomas exhibited an overall increased rate ofrecurrence, but between 15-20% benign meningiomaswill also exhibit an unfavourable clinical course withrecurrence before 10 years despite aggressive surgery.We investigated 247 cases of meningiomas grade I andII. The immunohistochemical expression of 30 differentmolecular biomarkers of cell adhesion molecules, cell-cycle and apoptosis regulators and checkpoints wasanalyzed. We also determined apoptosis by in-situhybridization (APOPDETEK™) and loss ofchromosome 1p36 by FISH. The study revealed astatistically significant co-variation (p<0.05) betweenmeningiomas grade II associated with severalclinicopathological features (Simpson grade of clinicalresection, necrosis, nuclear atypia, macronucleoli,transition to small cell, sheet-like growth, highcellularity), increased expression of several biomarkersof tumour proliferation (Cyclin A, Cyclin E, MIB-1 orMDM2), proteases (Cathepsin D) or cell-adhesion(CD44) and lower expression of progesterone receptorsthan meningiomas grade I. The presence of Psammomabodies or the location at convexity were protectiveprognostic factors for tumour recurrence while highcellularity and early age of onset (<57 year-old) wereindicators of increased recurrence risk. The expressionof COX-2, γ-catenin, Topoisomerase IIa, VEGF andMIB-1 was significantly higher in the cohort of recurrentmeningiomas. Meningiomas with chromosome 1p36 lossshowed a higher recurrence rate (33.3%) than meningiomas with normal chromosome 1p36 (18%).Increased COX-2 expression in recurrent meningiomamay also suggest a putative role of COX-2 inhibitors asa chemopreventive treatment for recurrence.