title: DNA topoisomerase I and II expression in drug resistant germ cell tumours.
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 alpha is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and II alpha 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 alpha expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and II alpha expression (P=0.004) and downregulation of topoisomerase II alpha 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.
authors.affiliation: Department of Histopathology and Morbid Anatomy, St Bartholomew's Hospital, Queen Mary's School of Medicine and Dentistry, London EC1 7BE, UK. D.Berney@bartsandthelondon.nhs.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: J
authors.initials: J
authors.lastname: Shamash
authors.forename: J
authors.initials: J
authors.lastname: Gaffney
authors.forename: S
authors.initials: S
authors.lastname: Jordan
authors.forename: R T D
authors.initials: RT
authors.lastname: Oliver
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018236:Carcinoma, Embryonal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018239:Seminoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013724:Teratoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000737:chemistry / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; D005047:Etoposide; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin