Expression of multidrug resistance-related protein (MRP-1), lung resistance-related protein (LRP) and topoisomerase-II (TOPO-II) in Wilms' tumor: immunohistochemical study using TMA methodology.
OBJECTIVE
MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse effects of various chemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT).


METHODS
TMA block was constructed from 14 samples of WT's and from xenografts derived from them. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa.


RESULTS
All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa. In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expression of LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIa expression and exhibited weak/negative staining of LRP.


CONCLUSIONS
This study shows that although all the proteins evaluated, had different expression patterns in the tumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications of these changes in expression and their relevance to the resistance of these tumors to chemotherapy requires further investigation. The finding of different expression profiles for the multidrug resistance proteins in the original WT's and their xenografts suggests that the results of animal cancer models may be difficult to interpret.
Fridman
Eduard
E
Departments of Pathology and Urology, Chaim Sheba Medical Center, Tel-Aviv University, Israel.
Skarda
Jozef
J
Pinthus
Jonatan H
JH
Ramon
Jonathan
J
Mor
Yoran
Y
D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D009396:Wilms Tumor / Q000188:drug therapy / Q000378:metabolism*; D000099187:Major Vault Protein
D004250:DNA Topoisomerases, Type II; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1