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

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