High topoisomerase IIα expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas

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 II alpha (topoII alpha), 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 topoII alpha 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 topoII alpha immunopositive cells protein expression varied from 0.0 to 49.1% (5.2 +/- 8.3%, mean +/- SD). In oligoastrocytomas, the mean topoII alpha 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 topoII alpha 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). TopoII alpha expression was not associated with the age or sex of patient, and the rate of apoptosis. TopoII alpha expression associated highly significantly with patient prognosis; a significantly higher proportion of patients with low rather than with high topoII alpha score was alive at the end of the 5-year follow-up (P = 0.03). Cox analysis was used to demonstrate that topoII alpha had an independent prognostic value for survival (P = 0.034). In conclusion, high topoII alpha expression characterizes oligodendrogliomas and oligoastrocytomas which are poorly differentiated, have high proliferation rate, and has prognostic value for overall survival of these patients. Therefore, topoII alpha may be a useful marker for better targeted selection of poor prognosis oligodendroglioma patients for adjuvant therapy.