Peroxisome Proliferator-Activated Receptor (PPAR) Expression Correlates With Tumor Grade and Prognostic Outcome in Meningiomas.

Abstract

The present study assessed the expression of different isoforms of PPAR, an important regulator of cell metabolism and proliferation, in meningiomas and correlated it with different clinicopathological variables and clinical outcomes. A total of 238 meningiomas were studied, including grade 1 (n=133), grade 2 (n=66), grade 3 (n=2), and brain-invasive otherwise benign meningiomas (BIOB) (n=37). The expression of PPAR-γ, phosphorylated PPAR-γ, and PPAR-β was assessed by immunohistochemistry. A semiquantitative grading was used to classify the cases into high and low expression. High nuclear and cytoplasmic immunoreactivity of PPAR-γ was significantly more frequent in grade 2 meningiomas than in grade 1 or BIOB ( P =0.023, 0.006 for nuclear expression, and 0.001, 0.004 for cytoplasmic expression, respectively). It was also associated with higher proliferative activity and p53 positivity ( P =0.002 and 0.001, respectively). Phosphorylated PPAR-γ and PPAR-β expression did not show any association with grade. PPAR-γ immunoreactivity, extent of resection, and histologic grade were associated with overall survival (OS) [ P =0.031 (nuclear)/0.005 (cytoplasmic), 0.002, and <0.001, respectively]. Interestingly, BIOB cases had OS similar to grade 2 tumors, significantly shorter than that of their grade 1 counterparts. Further, high PPAR-γ expression was associated with better outcomes with no death in patients who received adjuvant radiotherapy. The present study, for the first time, highlights that PPAR expression is implicated in the pathobiology of meningiomas and has prognostic implications, especially in cases receiving radiotherapy. Considering the availability of PPAR modulatory drugs, it may be an important therapeutic target. In addition, the meticulous examination of the brain invasion still holds significant promise for prognostication.