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

Purpose: To correlate the immunohistochemical expression of topoisomerase IIα (topoIIα) 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: I...

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Published in:Clinical cancer research 2008-03, Vol.14 (6), p.1759-1766
Main Authors: DOUSSIS-ANAGNOSTOPOULOU, Ipatia A, VASSILAKOPOULOS, Theodoros P, KAKLAMANIS, Loukas, PANAYIOTIDIS, Panayiotis, KYRTSONIS, Marie-Christine, ANDROULAKI, Athina, PATSOURIS, Efstratios, KITTAS, Christos, PANGALIS, Gerassimos A, THYMARA, Irini, KORKOLOPOULOU, Penelope, ANGELOPOULOU, Maria K, SIAKANTARIS, Marina P, KOKORIS, Styliani I, DIMITRIADOU, Evangelia M, KALPADAKIS, Christina, MATZOURANIS, Marina
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
doxorubicine
etoposide
Hematologic and hematopoietic diseases
Hodgkin's lymphoma
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Pharmacology. Drug treatments
prognostic factors
topoisomerase IIα
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Summary:Purpose: To correlate the immunohistochemical expression of topoisomerase IIα (topoIIα) 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 (topoIIα) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238. Results: The mean ± SD percentage of topoIIα- and Ki-67–positive Hodgkin-Reed-Sternberg (HRS) cells was 63 ± 19% (5%-98%) and 73 ± 19% (8%-99%), respectively. The median percentage of topoIIα-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoIIα expression and patient characteristics. TopoIIα and Ki-67 expression were correlated (Spearman's Rho 0.255, P < 0.001). TopoIlα 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 topoIIα expression was independently predictive of FFS. Conclusion: TopoIIα was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoIIα was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-07-1395