Topoisomerase IIalpha expression as an independent prognostic factor in Hodgkin's lymphoma.
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.
Doussis-Anagnostopoulou
Ipatia A
IA
Laboratory of Histology and Embryology, National and Kapodistrian University of Athens, Medical School, Athens, Greece. ipatiada@med.uoa.gr
Vassilakopoulos
Theodoros P
TP
Thymara
Irini
I
Korkolopoulou
Penelope
P
Angelopoulou
Maria K
MK
Siakantaris
Marina P
MP
Kokoris
Styliani I
SI
Dimitriadou
Evangelia M
EM
Kalpadakis
Christina
C
Matzouranis
Marina
M
Kaklamanis
Loukas
L
Panayiotidis
Panayiotis
P
Kyrtsonis
Marie-Christine
MC
Androulaki
Athina
A
Patsouris
Efstratios
E
Kittas
Christos
C
Pangalis
Gerassimos A
GA
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
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II