Topoisomerase II and IIß expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome

A J Lodge¹, A G Hall², M M Reid³, G G McIntosh⁴, M Steward⁴, J J Anderson¹, C H W Horne⁴ and B Angus¹

¹ Department of Pathology, University of Newcastle, Queen Victoria Road, Newcastle upon Tyne, NE2 4HH, UK
² Department of Paediatric Oncology, University of Newcastle
³ Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK
⁴ Novocastra Laboratories Ltd, Balliol Business Park West, Benton Lane, Longbenton, Newcastle upon Tyne, NE12 8EW, UK

Correspondence to:
Dr Lodge ajlodge{at}yahoo.co.uk

Background/Aims—Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II and IIß might be of predictive value in ALL.

Methods—Cellular expression of topoisomerases II and IIß was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II and IIß expression were assessed.

Results—Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II and IIß expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II expression was found to be related to sex, with expression being lower in girls (p = 0.002).

Conclusions—These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II and IIß expression as defined by immunohistochemistry.

Key Words: topoisomerase • leukaemia • prognosis • immunohistochemistry

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