DNA topoisomerase II alpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

Aims: To assess the value of topoisomerase Hot (TopoII alpha) as a novel pr oliferation-associated molecule, by correlating its immunohistochemical exp ression with Ki67 MIB-1), cell proliferating cell nuclear antigen (PCNA) an d mitotic index in meningiomas. Furthermore. to investigate its relation to standard clinicopathological parameters and patients' outcome. Methods and results: This retrospective study comprised a consecutive serie s of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archi val formalin-fixed paraffin-embedded sections were stained with standard im munohistochemical methods. The lower proliferation indices were obtained wi th TopoII alpha( and the higher ones with PCNA. TopoII alpha labelling inde x (LI) ranged from 0.1% to 10%, (median 0.5%) and, along with K167 and PCNA LI, increased with malignancy grade (P = 0.049, P = 0.045 and P < 0.001. r espectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoII<alpha> and Ki67 (P < 0.001) or PCNA (P = 0.032). In univariate and multivariate survival an alysis, TopoII<alpha> failed to predict meningioma recurrence and did not a ffect disease-free survival. Only tumour size and Ki67 LI provided signific ant prognostic information in this regard. Conclusions: TopoII alpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers curr ently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However. it fails to dis criminate between benign and atypical neoplasms and does not provide progno stic information beyond that obtained by Ki67.