Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
OBJECTIVE: 5-Lipoxygenase (5-LO) oxidizes arachidonic acid into proinflammatory eicosanoids that may promote tumorigenesis. In this study, we investigated whether 5-LO is expressed in human astrocytomas and what effect its expression may have on patient outcome. METHODS: Increased 5-LO messenger ribonucleic acid and protein expression was detected by the polymerase chain reaction and antibody-based approaches, respectively, in surgical astrocytoma specimens and established glioblastoma multiforme cell lines compared with primary cell culture from the human white matter. RESULTS: Immunohistochemical analysis revealed predominantly nuclear 5-LO staining in 44 of 49 glioblastoma multiforme samples (90%), 8 of 10 (80%) anaplastic astrocytomas samples, and 3 of 13 (23%) low-grade astrocytoma samples analyzed. Double-staining experiments with anti-CD-68 (macrophage/microglial marker) and anti-5-LO antibodies suggest that both CD-68-positive and CD-68-negative tumor cells express 5-LO protein. Staining of 5-LO was significantly more frequent in high-grade than in low-grade tumors (P = 0.001). Patients whose tumors expressed 5-LO were significantly older, had lower preoperative Karnofsky performance scores and shorter survival than patients whose tumors did not express 5-LO. After adjusting for pathological diagnosis and age, respectively, neither Karnofsky performance score nor survival were significantly associated with 5-LO staining. CONCLUSION: These data indicate that 5-LO is overexpressed in high-grade astrocytomas and supports the idea that eicosanoids may play a role in tumorigenesis of these brain tumors.
