title: DNA topoisomerase IIalpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas.
abstract: OBJECTIVE
  To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome.
  
  
  RESULTS
  This retrospective study comprised a consecutive series 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). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard.
  
  
  CONCLUSIONS
  TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.
authors.affiliation: Department of Pathology, National and Kapodistrian University of Athens, Greece. takonst@hol.gr
authors.forename: A E
authors.initials: AE
authors.lastname: Konstantinidou
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
authors.forename: P
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: N
authors.initials: N
authors.lastname: Kavantzas
authors.forename: H
authors.initials: H
authors.lastname: Mahera
authors.forename: P
authors.initials: P
authors.lastname: Davaris
mesh_terms: D000951:Antigens, Neoplasm; D002455:Cell Division / Q000502:physiology*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013223:Statistics as Topic; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D004250:DNA Topoisomerases, Type II