1. ¹Department of Histopathology and Morbid Anatomy, St Bartholomew's Hospital, Queen Mary's School of Medicine and Dentistry, London EC1 7BE, UK
2. ²Department of Medical Oncology, St Bartholomew's Hospital, Queen Mary's School of Medicine and Dentistry, London EC1 7BE, UK

Correspondence: D M Berney, E-mail: D.Berney@bartsandthelondon.nhs.uk

Received 18 January 2002; Revised 21 May 2002; Accepted 23 May 2002.

Abstract

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase II is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and II were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase II expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and II expression (P=0.004) and downregulation of topoisomerase II after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits.