The topoisomerase IIalpha expression correlates with survival in patients with advanced Hodgkin's lymphoma.
OBJECTIVE
Topoisomerase (Topo) II isoenzymes are the targets for drugs, such as epidophyllotoxins and doxorubicin. The aim of this study was to determine whether the expression of Topo IIalpha and Ki67 in advanced Hodgkin's disease (HD) played a role as a prognostic factor or predictor of response to treatment.


METHODS
Forty-two patients who were homogeneously treated and had a long-term follow-up were selected for the study. Immunohistochemistry of paraffin-embedded tissue sections was performed. The effect of patient and tumor characteristics on failure-free survival (FFS) and overall survival were evaluated in a univariate analysis using the Cox proportional hazards model. The Cox model was also implemented in a multivariate analysis using stepwise selection.


RESULTS
Positive nuclear staining for Topo IIalpha in Reed-Stemberg or Reed-Stemberg variant cells was seen in 90% of HD cases, and coexpression of Ki67 and Topo IIalpha in 79%. No significant difference in the percentage of Topo IIalpha-positive cells was detected among histological HD subtypes. In the univariate analysis for FFS, the male gender, high lactate dehydrogenase, and Topo IIalpha < 30% were associated with more relapses. In the multivariate analysis for FFS, only Topo IIalpha < 30% was statistically associated with shorter FFS, with relative risk of 3 (95% confidence interval, 1.26-7.15; P = 0.013). In uni- and multivariate analyses for overall survival, only Topo IIalpha was associated with shorter survival.


CONCLUSIONS
Topo IIalpha expression could be useful in advanced HD to identify patients with a higher risk of relapse and lesser overall survival. It is of potential utility in the design of specific treatments.
Provencio
Mariano
M
Department of Medical Oncology, University Hospital Puerta de Hierro, E-28035 Madrid, Spain. mprovencio@seom.org
Corbacho
Cesar
C
Salas
Clara
C
Millan
Isabel
I
Espana
Pilar
P
Bonilla
Felix
F
Ramon Cajal
Santiago
S
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm; D002648:Child; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D012008:Recurrence; D013997:Time Factors
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D020033:Protein Isoforms; D004250:DNA Topoisomerases, Type II