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Cyclooxygenase-2 (COX-2) expression in human meningioma: correlation with malignant progression and potential target
Changching D Lin, Lawrence Kenyon, Terry Hyslop, Elizabeth Hammond, David W Andrews, Walter J Curran Jr., Adam P Dicker, Jefferson Medical College, Philadelphia, PA; Latter Day Saints Hospital, Salt Lake City, UT.
Meningiomas are one of the most common central nervous system tumors, with an annual incidence in the U.S. of approximately 3-6 per 100,000 people. The high recurrence rate in partially resected meningiomas has led to the use of additional adjuvant therapy designed to increase tumor control. To date, there are few molecular markers that have been identified that may also serve as potential targets for therapy. COX-2 is up-regulated in a number of epithelial tumors, however, there are no published reports regarding the expression of COX-2 in meningioma. This study evaluated a possible relationship between COX-2 expression and malignant progression of meningioma. After IRB approval, 83 surgical cases were classified according to the old WHO criteria. COX-2 stained slides were scored by two observers and an immuno-histochemical score (IHS) was calculated and analyzed for statistical significance. The analyses are based on a continuous score of expression, which is the product of intensity and percentage of expression. COX-2 was considered as an ordinal categorical variable, and the tumor characteristic (benign, superficially invasive, atypical, and malignant) as a second ordinal variable. For testing hypotheses of an ordinal-by-ordinal nature, the Jonckheere-Terpstra test (Hollander and Wolfe) was used in addition to the Kruskal-Wallis test, which does not assume order of the groups being compared. All computations were completed in StatXact 4.0. The association between tumor characteristic and Cox-2 expression is highly significant (p =0.012). Tumors with a more malignant phenotype (benign - superficially - invasive - atypical malignant) are associated with increasingly higher levels of COX-2. If the ordering of the categories "superficially invasive" and "atypical" was switched, the association between tumor characteristic and COX-2 expression is still significant (p=0.022). The association of COX-2 and meningioma phenotype is unique and represents a potential area for therapeutic intervention with selective COX-2 inhibitors, either alone or in combination with radiation therapy.