title: High topoisomerase IIalpha expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas.
abstract: The role of molecular markers predicting the prognosis and the selection of patients for further adjuvant therapies is not well established in oligodendroglioma patients. A potential prognostic as well as a therapeutically predictive factor, topoisomerase IIalpha (topoIIalpha), is a molecular target for certain cytotoxic drugs. Its expression has been shown to correlate with the prognosis in a number of different cancers and with the chemosensitivity of cancer cells in vitro. The expression of topoIIalpha was evaluated immunohistochemically in 59 oligodendrogliomas and in 29 mixed gliomas with a predominating oligodendroglioma component by the use of a tissue microarray technique. In the gliomas, the percentage of topoIIalpha immunopositive cells protein expression varied from 0.0 to 49.1% (5.2 +/- 8.3%, mean+/- SD). In oligoastrocytomas, the mean topoIIalpha score was significantly higher in the oligodendroglioma than in the astrocytoma component of the tumour (5.37 +/- 5.58% vs. 1.89 +/- 2.49%, P = 0.018). A significant association was found between the high proportion of topoIIalpha positive cells and high grade of the tumour (P < 0.0001), high tumour proliferation rate (P < 0.0001), p53 overexpression (P = 0.01) and high expression of tumour suppressing retinoblastoma protein (P = 0.023). TopoIIalpha expression was not associated with the age or sex of patient, and the rate of apoptosis. TopoIIalpha expression associated highly significantly with patient prognosis; a significantly higher proportion of patients with low rather than with high topoIIalpha score was alive at the end of the 5-year follow-up (P = 0.03). Cox analysis was used to demonstrate that topoIIalpha had an independent prognostic value for survival (P = 0.034). In conclusion, high topoIIalpha expression characterizes oligodendrogliomas and oligoastrocytomas which are poorly differentiated, have high proliferation rate, and has prognostic value for overall survival of these patients. Therefore, topoIIalpha may be a useful marker for better targeted selection of poor prognosis oligodendroglioma patients for adjuvant therapy.
authors: Department of Pathology, Tampere University Hospital, Tampere, Finland.blhemi@uta.fi
authors: H E
authors: HE
authors: Miettinen
authors: T A
authors: TA
authors: Järvinen
authors: U
authors: U
authors: Kellner
authors: P
authors: P
authors: Kauraniemi
authors: R
authors: R
authors: Parwaresch
authors: I
authors: I
authors: Rantala
authors: H
authors: H
authors: Kalimo
authors: L
authors: L
authors: Paljärvi
authors: J
authors: J
authors: Isola
authors: H
authors: H
authors: Haapasalo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D017209:Apoptosis; D001254:Astrocytoma / Q000201:enzymology / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D002648:Child; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D009837:Oligodendroglioma / Q000201:enzymology* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D004250:DNA Topoisomerases, Type II