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Background  Matrix metalloproteinases ( MMP s) and tissue inhibitors of metalloproteinases ( TIMP s) are considered to be key mediators of tumor invasion and metastasis.  MMP ‐2 and  MMP ‐9 are expressed in meningiomas of dogs, but  TIMP  expression, and variations of specific  MMP / TIMP  ratios still are unknown in this tumor.    Hypothesis/Objectives  Expression of  MMP / TIMP  might increase progressively from grade I to grade  III  meningioma. Therefore, genetic expression of  MMP ‐2 and  MMP ‐9, and specific  TIMP ‐2 and  TIMP ‐1, respectively, has been investigated in meningiomas of different grades.    Animals  Selected formalin‐fixed paraffin‐embedded tissue from 43 meningiomas of dogs was evaluated.    Methods  Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real‐time polymerase chain reaction ( RT ‐ qPCR ).    Results   MMP ‐9 was not expressed in all of the tumors, but  MMP ‐2 was significantly more expressed in papillary meningioma. Likewise, the  MMP ‐2/ TIMP ‐2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma,  TIMP ‐1 gene expression was significantly higher than in grades I and  III .    Conclusions and Clinical Importance   MMP ‐2/ TIMP ‐2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs.  TIMP ‐1 expression may play a role independent of  MMP ‐9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans.

Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs