Evaluation of DNA topoisomerase IIalpha expression provides independent prognostic information in non-Hodgkin's lymphomas.
OBJECTIVE
In view of the dual role that DNA topoisomerase IIa (TopoIIa) plays as a cell proliferation marker and as a possible indicator of chemosensitivity, we investigated its expression in non-Hodgkin's lymphomas (NHL) in relation to conventional clinicopathological parameters, cell proliferation (as defined by Ki67 immunoreactivity), response to therapy and patient outcome.


RESULTS
Formalin-fixed paraffin-embedded tissues from 153 patients with NHL were immunohistochemically stained for TopoIIalpha. Patients were followed up until death (n = 63) or for an average of 68 months (median 64 months, n = 90). The percentage of TopoIIalpha positive cells (TopoIIalpha LI) increased with grade (P < 0.001), extranodal location (P = 0.05) and Ki67 LI (P = 0.01, r = 0.673). In most cases (58%), Ki67 LI exceeded TopoIIalpha LI (TopoIIalpha/Ki67 < 1), especially within the indolent group (P < 0.001). TopoIIalphaLI, Ki67LI and TopoIIalpha/Ki67 ratio were all adversely related to overall survival in univariate analysis, though their significance was not maintained after adjustment for grade. In multivariate analysis high TopoIIalpha/Ki67 ratio and high TopoIIalpha LI independently predicted shortened overall and post-relapse survival, respectively. Most importantly, low TopoIIalpha/Ki67 ratio was the only independent predictor of diminished disease-free survival. However, there was no relationship between TopoIIalpha expression and response.


CONCLUSIONS
Our results suggest that evaluation of TopoIIalpha expression and TopoIIalpha/Ki67 ratio as cell proliferation markers provides independent prognostic information in relation to post-relapse and overall survival. Furthermore, TopoIIalpha/Ki67 ratio appears to play a key role in the identification of patients prone to early relapse.
Korkolopoulou
P
P
Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece. pkorkol@cc.uoa.gr
Angelopoulou
M
M
Siakantari
M
M
Mitropoulos
F
F
Vassilakopoulos
T
T
Zorzos
H
H
Rassidakis
G
G
Androulaki
A
A
Patsouris
E
E
Kittas
C
C
Davaris
P
P
Pangalis
G A
GA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II