title: Topoisomerase IIalpha expression as an independent prognostic factor in Hodgkin's lymphoma.
abstract: OBJECTIVE
  To correlate the immunohistochemical expression of topoisomerase IIalpha (topoIIalpha) in Hodgkin's lymphoma (HL) with clinicopathological parameters, the expression of Ki-67 and the outcome of patients, who had been homogenously treated with ABVD or equivalent regimens.
  
  
  METHODS
  Immunohistochemistry using the monoclonal antibody Ki-S1 (topoIIalpha) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238.
  
  
  RESULTS
  The mean +/- SD percentage of topoIIalpha- and Ki-67-positive Hodgkin-Reed-Sternberg (HRS) cells was 63 +/- 19% (5%-98%) and 73 +/- 19% (8%-99%), respectively. The median percentage of topoIIalpha-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoIIalpha expression and patient characteristics. TopoIIalpha and Ki-67 expression were correlated (Spearman's Rho 0.255, P < 0.001). TopoIlalpha expression within the highest quartile of this patient population was predictive of failure free survival (FFS) (10-year rates 82 +/- 3% vs 68 +/- 7%, P = 0.02 for patients falling into the quartiles 1-3 and 4 respectively). In multivariate analysis topoIIalpha expression was independently predictive of FFS.
  
  
  CONCLUSIONS
  TopoIIalpha was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoIIalpha was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.
authors.affiliation: Laboratory of Histology and Embryology, National and Kapodistrian University of Athens, Medical School, Athens, Greece. ipatiada@med.uoa.gr
authors.forename: Ipatia A
authors.initials: IA
authors.lastname: Doussis-Anagnostopoulou
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.forename: Irini
authors.initials: I
authors.lastname: Thymara
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
authors.forename: Marina P
authors.initials: MP
authors.lastname: Siakantaris
authors.forename: Styliani I
authors.initials: SI
authors.lastname: Kokoris
authors.forename: Evangelia M
authors.initials: EM
authors.lastname: Dimitriadou
authors.forename: Christina
authors.initials: C
authors.lastname: Kalpadakis
authors.forename: Marina
authors.initials: M
authors.lastname: Matzouranis
authors.forename: Loukas
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Panayiotidis
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kyrtsonis
authors.forename: Athina
authors.initials: A
authors.lastname: Androulaki
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Christos
authors.initials: C
authors.lastname: Kittas
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II