DNA Topoisomerase IIa in Multiple Myeloma: A Marker of Cell Proliferation and Not Drug Resistance

DNA Topoisomerase IIa in Multiple Myeloma: A Marker of Cell Proliferation and Not Drug Resistance

DNA topoisomerase IIa (topo IIa) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo IIa is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study...

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Veröffentlicht in:Modern pathology 2001-09, Vol.14 (9), p.886-891
Hauptverfasser: Wilson, Carla S, Medeiros, LJeffrey, Lai, Raymond, Butch, Anthony W, McCourty, Althea, Kelly, Kathy, Brynes, Russell K
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container_issue 9
container_start_page 886
container_title Modern pathology
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creator Wilson, Carla S
Medeiros, LJeffrey
Lai, Raymond
Butch, Anthony W
McCourty, Althea
Kelly, Kathy
Brynes, Russell K
description DNA topoisomerase IIa (topo IIa) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo IIa is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo IIa is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo IIa is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo IIa. Immunoreactivity with an addi- tional marker of drug resistance, glutathione-S-transferase p, and the proliferation marker Ki-67 were also examined. Topo IIa was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P
doi_str_mv 10.1038/modpathol.3880407
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Down-regulation of this enzyme is one form of drug resistance. Topo IIa is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo IIa is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo IIa is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo IIa. Immunoreactivity with an addi- tional marker of drug resistance, glutathione-S-transferase p, and the proliferation marker Ki-67 were also examined. Topo IIa was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P &lt;.001). A role for drug resistance could not be supported, given this strong relationship with proliferation and the finding that glutathione-S-transferase p expression in 57 (78%) cases was independent of topo IIa immunoreactivity. Topo IIa was identified in 91 to 100% of highly proliferative tumors, as evaluated by bromodeoxyuridine uptake or Ki-67 reactivity, respectively. Proliferation also correlated with the histologic grade of the MM. Therefore, topo IIa immunoreactivity is primarily a marker of cell proliferation in MM and as such is likely to have prognostic significance. 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