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Topoisomerase II Expression as an Independent Prognostic Factor in Hodgkin's Lymphoma

Authors' Affiliations: ¹ Laboratory of Histology and Embryology, ² First Department of Internal Medicine and Department of Haematology and ³ Department of Pathology, National and Kapodistrian University of Athens, Medical School, Athens, Greece

Requests for reprints: Ipatia Doussis-Anagnostopoulou, Laboratory of Histology and Embryology, Athens Medical School, 75, Micras Asias str., 11527 Goudi, Athens, Greece. Phone: 0030-210-7462348/0030-210-6717049; E-mail: ipatiada{at}med.uoa.gr.

Purpose: To correlate the immunohistochemical expression of topoisomerase II (topoII) 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.

Experimental Design: Immunohistochemistry using the monoclonal antibody Ki-S1 (topoII) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238.

Results: The mean ± SD percentage of topoII- and Ki-67–positive Hodgkin-Reed-Sternberg (HRS) cells was 63 ± 19% (5%-98%) and 73 ± 19% (8%-99%), respectively. The median percentage of topoII-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoII expression and patient characteristics. TopoII and Ki-67 expression were correlated (Spearman's Rho 0.255, P < 0.001). TopoIl 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 topoII expression was independently predictive of FFS.

Conclusion: TopoII was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoII was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.