Cyclooxygenase-2 (COX-2) overexpression in childhood brain tumors

The overexpression of COX enzymes has been demonstrated in human neoplasms at various sites, including the colon, gastrointestinal tract, lung, skin and recently in brain tumors. In this study, COX-2 receptor overexpression in primary childhood brain tumors was determined and the distribution pattern of COX-2 receptors was examined. A sensitive, 4-step, alkaline phosphatase conjugated antigen detection technique was used and a specific monoclonal antibody for medulloblastomas/ primitive neuroectodermal tumors (MEDs/PNETs), anaplastic, high-grade astrocytomas (ASTRs) and in glioblastoma multiformes (GMs) was employed. All of the 14 MEDs/PNETs observed demonstrated high levels of immunoreactivity (overexpression), with the highest immunostaining intensity (grades A and B). However, of the 14 subtypes of astrocytic tumors examined, the COX-2 receptor expression level did not even approach those of the MEDs/PNETs levels. However, significant differences were found when comparing low grade pilocytic ASTRs to high grade anaplastic ASTRs and glioblastomas. In two low grade pilocytic ASTRs, the expression level never exceeded 20%, while in high grade glial tumors (6 anaplastic ASTRs and 6 GMs) 30 to 50% of the tumor cells overexpressed COX-2 receptors, documenting an increase in COX-2 receptor overexpression with the increasing grade of the astrocytic tumor. In view of these findings, it would appear likely that COX-2 inhibitors may represent a chemo-preventive tool in treating childhood brain tumors, which are the leading cause of solid tumor cancer death in children under the age of 20.