Cyclooxygenase-2 expression in astrocytomas. Relationship with microvascular parameters, angiogenic factors expression and survival.
OBJECTIVE
Cyclooxygenase-2 (COX-2) is the enzyme isoform involved in the synthesis of prostaglandins (PGs) and thromboxane from arachidonic acid. The role of the up-regulation of COX-2 in the formation and progression of gliomas has been dealt with in earlier reports, which describe increased levels of PGs within gliomas. In the present study, we examined the expression of COX-2 in diffuse gliomas of astrocytic origin in relation to microvascular parameters, angiogenic factors and survival.


METHODS
A total of 83 cases of diffuse astrocytomas (grade II-IV) were analyzed by immunohistochemistry for the presence of COX-2.


RESULTS
COX-2 expression was detected in 79 cases (95%) with an increased expression in grade IV as compared to grades II/III (p=0.024). A positive correlation occurred between COX-2 and angiogenic factors such as vascular endothelial growth factor (VEGF) (p<0.0001) and hypoxia inducible factor (HIF)-1alpha (p=0.005), as well as the tumours' proliferative activity (expressed as the percentage of Ki-67 positive cells) (p=0.032), and total vascular area (TVA) (p=0.040). In univariate analysis, COX-2 was associated with shortened survival (p = 0.050). Multivariate survival analysis showed that the interaction model of COX-2 with grade along with age were the only significant prognostic indicators.


CONCLUSIONS
These results implicate COX-2 in the angiogenesis and biological aggressiveness of diffuse astrocytomas, and suggest that it would be worthwhile to examine how the inhibition of COX-2 expression may influence astrocytoma patients' survival.
Perdiki
Marina
M
Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece. marinaperdiki@hotmail.com
Korkolopoulou
Penelope
P
Thymara
Irene
I
Agrogiannis
George
G
Piperi
Christina
C
Boviatsis
Efstathios
E
Kotsiakis
Xenophon
X
Angelidakis
Dimitrios
D
Diamantopoulou
Kalliopi
K
Thomas-Tsagli
Euphemia
E
Patsouris
Efstratios
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D001254:Astrocytoma / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human