Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.
METHODS
Aetiology (case series) Level of Evidence 4.


OBJECTIVE
To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal.


METHODS
The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy.


RESULTS
Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC.


CONCLUSIONS
This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.
Schaeffer
Edward M
EM
The James Buchanan Brady Urologic Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. eschaef4@jhmi.edu
Guzzo
Thomas J
TJ
Furge
Kyle A
KA
Netto
George
G
Westphal
Michael
M
Dykema
Karl
K
Yang
Ximing
X
Zhou
Ming
M
Teh
Bin Tean
BT
Pavlovich
Christian P
CP
D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018276:Carcinoma, Medullary / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D008297:Male; D009392:Nephrectomy; D011379:Prognosis; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome; D055815:Young Adult
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II