Possible role of matrix metalloproteinase in osteolytic intracranial meningiomas

Abstract

Objective: Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma.

Methods: Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcription-quantitative PCR analysis (RT-PCR) and immunohistochemical analysis.

Results: Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP-9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed.

Conclusion: Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.

Keywords: Matrix metalloproteinase; Meningioma; Osteolytic.

Fig. 1

Radiologic findings. A : Severe destruction group : convexity meningioma. B : Severe destruction group : parasagittal meningioma. C : Moderate destruction group : olfactory groove meningioma. D : Moderate destruction group : convexity meningioma. E : Mild destruction group : convexity meningioma. F : Mild destruction group : parasagittal meningioma.

Fig. 2

Operative findings. A : Severe destruction with extensive osteolysis of the skull. B : Moderate destruction into the skull. C : Mild destruction into the diploic space and the inner table within the skull.

Fig. 3

Results of gelatin zymography and reverse transcription-quantitative PCR analysis (RT-PCR) in the severe and mild destruction groups. A : Gelatin zymography, B : RT-PCR; The expression of matrix metalloproteinase (MMP) -2 activity is higher in the extradural masses than in the intradural masses. The expression of MMP-9 is higher in the intradural masses than in the extradural masses (One case with severe destruction was not divided into intra and extradural portion).

Fig. 4

Results of gelatin zymography and reverse transcription-quantitative PCR analysis (RT-PCR) in the moderate destruction group. A : Gelatin zymography, B : RT-PCR; Extradural masses show higher levels of matrix metalloproteinase (MMP)-2 and MMP-9 expression when compared with intradural masses.

Fig. 5

Immunohistochemical staining with matrix metalloproteinase (MMP)-2 and MMP-9. A and B : The extradural mass was immunopositive, and the immunopositivity for MMP-2 is observed adjacent to the osteolytic bone (Original magnification ×200). C and D : A few MMP-9-positive staining is noted adjacent to the osteolytic bone (Original magnification ×200).