Cyclooxygenase-2 expression in astrocytomas. Relationship with microvascular parameters, angiogenic factors expression and survival
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.
Materials and methods
A total of 83 cases of diffuse astrocytomas (grade II–IV) were analyzed by immunohistochemistry for the presence of COX-2.
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)-1α (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.
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.
Keywordsastrocytoma hypoxia HIF-1α VEGF COX-2
Unable to display preview. Download preview PDF.
- 13.Piazza GA, Rahm AK, Finn TS, Fryer BH, Li H, Stoumen AL, Pamukcu R, Ahnen DJ (1997) Apoptosis primarily accounts for the growth-inhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction Cancer Res 57(12):2452–2459PubMedGoogle Scholar
- 18.Matsuo M, Yonemitsu N, Zaitsu M, Ishii K, Hamasaki Y, Fukuyama K, Tabuchi K, Miyazaki S (2001) Expression of prostaglandin H synthase-2 in human brain tumors Acta Neuropathol (Berl) 102(2):181–187Google Scholar
- 26.Korkolopoulou P, Patsouris E, Konstantinidou AE, Pavlopoulos PM, Kavantzas N, Boviatsis E, Thymara I, Perdiki M, Thomas-Tsagli E, Angelidakis D, Rologis D, Sakkas D (2004) Hypoxia-inducible factor 1alpha/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis Neuropathol Appl Neurobiol 30(3):267–278PubMedCrossRefGoogle Scholar
- 27.Cavenee WKFF, Nagane M, Huang H-JS, Newcomb EW, Bigner D, Weller M, Berens ME, Plate KH, Israel MA, Noble MD, Kleihues P (2000) Diffusely infiltrating astrocytomas. In: P Kleihues, Cavenee WK (eds) International Agency for Research on Cancer. Pathology and Genetics of Tumours of the Nervous System. IARC Press, Lyon, pp 10–21Google Scholar
- 28.Korkolopoulou P, Patsouris E, Kavantzas N, Konstantinidou AE, Christodoulou P, Thomas-Tsagli E, Pananikolaou A, Eftychiadis C, Pavlopoulos PM, Angelidakis D, Rologis D, Davaris P (2002) Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms Neuropathol Appl Neurobiol 28(1):57–66PubMedCrossRefGoogle Scholar
- 29.Shrieve DC, Alexander E 3rd, Black PM, Wen PY, Fine HA, Kooy HM, Loeffler JS (1999) Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome J Neurosurg 90(1):72–77PubMedCrossRefGoogle Scholar
- 34.Dassesse T, de Leval X, de Leval L, Pirotte B, Castronovo V, Waltregny D: Activation of the thromboxane A(2) pathway in human prostate cancer correlates with tumor Gleason score, pathologic stage. Eur Urol, 2006, Feb 23 (Epub ahead of print)Google Scholar
- 43.Fosslien E (2000) Escape from immunological surveillance in blastocyst implantation and cancer Ann Clin Lab Sci 30:111–112Google Scholar