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The Topoisomerase II Expression Correlates with Survival in Patients with Advanced Hodgkin’s Lymphoma

Departments of Medical Oncology [M. P., P. E., F. B.], Pathology [C. C., C. S., S. R. C.], and Bioestatistical [I. M.], University Hospital "Puerta de Hierro," E-28035 Madrid, Spain

Purpose: 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 II and Ki67 in advanced Hodgkin’s disease (HD) played a role as a prognostic factor or predictor of response to treatment.

Experimental Design: 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 II in Reed-Stemberg or Reed-Stemberg variant cells was seen in 90% of HD cases, and coexpression of Ki67 and Topo II in 79%. No significant difference in the percentage of Topo II-positive cells was detected among histological HD subtypes. In the univariate analysis for FFS, the male gender, high lactate dehydrogenase, and Topo II < 30% were associated with more relapses. In the multivariate analysis for FFS, only Topo II < 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 II was associated with shorter survival.

Conclusions: Topo II 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.

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