Increased expression of 5-lipoxygenase in high-grade astrocytomas.
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.


CONCLUSIONS
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.
Nathoo
Narendra
N
Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Prayson
Richard A
RA
Bondar
Judy
J
Vargo
Linda
L
Arrigain
Susana
S
Mascha
Edward J
EJ
Suh
John H
JH
Barnett
Gene H
GH
Golubic
Mladen
M
D000328:Adult; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000201:enzymology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase