Expression of topoisomerase IIIα in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody

Abstract

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcription. These enzymes are also the cellular targets of certain classes of chemotherapeutic agents termed topoisomerase poisons. A new human topoisomerase isoform, IIIα, was discovered in 1996, which is thought to have roles in genome stability and possibly chromosome separation during mitosis. It is possible that novel or existing anti-topoisomerase agents target topoisomerase IIIα, suggesting that this enzyme may have potential as a prognostic marker and chemotherapeutic target. In order to study expression patterns of topoisomerase IIIα we have produced a novel monoclonal antibody to human topoisomerase IIIα (TOPO3a-1A4), and used it to assess topoisomerase IIIα expression in a wide range of normal and neoplastic tissues. We have found that topoisomerase IIIα is expressed in a wide range of tissue types, with especially high concentrations in endothelial cells and stromal fibroblasts. No general relationship was observed between expression of topoisomerase IIIα and proliferation. Expression in neoplastic tissues often paralleled their normal counterparts, although certain tumours showed either increased (e.g. colonic adenoma) or reduced (e.g, gastric carcinoma. small cell carcinoma of bronchus) expression. If topoisomerase IIIα is found to be a target for chemotherapeutic agents, clinical response in different tumour types may be related to topoisomerase IIIα expression, which may be assessed using TOPO3a-1A4. (C) 2000 Cancer Research Campaign.