IMMUNOHISTOCHEMICAL EXPRESSION OF MMP-9 AND VEGF IN BENIGN AND MALIGNANT BRAIN MENINGIOMAS

Introduction. M eningiom as o f the brain are generally benign slow grow ing tumors w ith favorable outcom e, but in som e cases they can recur and demonstrate unpredictable course, despite their ben ign h istological structure. A ccor­ ding to the classification o f CNS tumors g iven by W HO 2007 edition, h isto logical m alignancy grade and proliferation index are one o f the m ost important predictors o f recurrence rate [1,2]. O n the other hand, the extent o f surgical resection is also an important factor, influencing on the risk o f recur­ rence, w hich in turn depend upon the tumor localization, its relation to the adjacent anatom ical structures, extent o f invasion and peritumoral brain edem a [2,3]. Little is know n about m echanism s o f m eningiom as invasion into the surrounding structures to date. It is b elieved that expression o f matrix m etalloproteinases (M M Ps) can be related w ith this process, especially the matrix m etalloproteinase o f 9 type (M M P-9) [4,5]. Matrix m etalloproteinases are able to degrade proteins o f extracellular matrix and basem ent membranes, p laying the defining role in invasion and m etastasis. The role o f M M Ps in invasion and m etastasis o f prostate, breast and lung cancer is reported in recent studies [6,7]. The tendency o f increased expression o f M M P-9 w ith increasing grade was revealed in m eningiom as [8, 9]. Except the determinant influence on the invasive abilities o f m eningiom as, M M P-9 also has important relation to the neoangiogenesis. The growth o f the tum or and its progression depends upon the form ation new capillary network to the great extent, w hich happens because o f secretion o f different angiogenic substances by the tumor tissue and underlies the so called “angiogenic sw itch” [6,10]. M M P-9 is one o f the crucial proangiogenic m olecules, w hich induces this event in m any neoplasm s, especially in m eningiom as [5,9,10]. M M P-9 causes not only the degradation o f the co llagen IV in basem ent membranes, w hich prom otes invasion and migration o f endothelial cells, but also has an equally important indirect effects on the induction o f new m icrovessel form ation from preexisting capillaries. One o f the m echanism s underlying the “angiogenic sw itch” is m obilization and activation o f the angiogenic m itogens from matrix stores, this process is facilitated by M M P-9, w hich acts as an exceptionally potent nanomolar angiogenic factor, releasing vascular endothelial growth factor (VEGF) from matrices [6, 9]. The results o f researches concerning the expression o f MM P-9 and VEGF in benign and malignant meningiomas are controversial. Many authors directed their search towards detection o f the relation between expression o f MM P-9 and invasion or tumor grade or between expression o f MM P-9 and microvessel density [5,9]. By the way, special attention should be devoted to the positive induction o f neoangiogenesis caused by MM P-9 in case o f growth factors recruitment, such as VEGF. Goal: determination o f the expression level o f MMP-9 and VEGF in different subtypes o f benign meningiomas and in anaplastic brain meningiomas, to establish the correlation between these markers. M aterials and methods. A ll specimens involved in this study were collected from 36 patients treated by neurosurgi­ cal resection o f meningiomas. The age range w as 25 to 75 years. A ll benign m eningiom as revealed location on the convexity o f the cerebral hemisphere. A m ong anaplastic m eningiom as 60% had convexity location, 20% suprasubtentorial and 20% parasagittal. In the sam ples w e studied, 26 cases were benign m eningiomas (grade I), among them 8 m eningiom as were represented by m eningothelial subtypes (n=8), 8 m eningiom as by fibroblastic (n=8),