title: Expression of multidrug resistance-associated proteins in rhabdomyosarcomas before and after chemotherapy: the relationship between lung resistance-related protein (LRP) and differentiation.
abstract: Rhabdomyosarcomas generally respond well to chemotherapy, and the residual lesions often are better differentiated than their primaries. This phenomenon may be explained by selective multidrug resistance (MDR) of differentiated tumor cell populations. We assess the role of MDR proteins in chemotherapy-induced differentiation in rhabdomyosarcomas in a clinical setting. Paraffin-embedded samples of 13 pairs of primary untreated rhabdomyosarcomas and their residual, recurrent, or metastatic lesions after chemotherapy were assessed for expression of MDR proteins, including P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP-1), and lung resistance-related protein (LRP). Expression was semiquantitatively scored based on the percentage of isolated immunoreactive tumor cells as follows: 0, negative; 0.5, <5%; 1, 5% to 25%; 2, 26% to 50%; 3, 51% to 75%, and 4, >75%. All specimens after chemotherapy, except the late recurrences, were better differentiated than their primary, untreated specimens. Pgp or MRP-1 expression did not change significantly, but LRP expression increased significantly after chemotherapy. In both untreated and treated samples, LRP was expressed primarily in differentiated cells. The findings indicate that the in vivo expression of LRP, but not of Pgp and MRP-1, is induced by chemotherapeutic treatment in rhabdomyosarcomas. The preferential expression of LRP in differentiated cells and the subsequent more extensive expression after chemotherapy suggests that LRP plays a role in therapy-induced differentiation.
authors.affiliation: Department of Pathology, University Hospital of Groningen, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Klunder
authors.forename: R
authors.initials: R
authors.lastname: Komdeur
authors.forename: W T A
authors.initials: WT
authors.lastname: Van Der Graaf
authors.forename: E J S M
authors.initials: EJ
authors.lastname: De Bont
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: E
authors.initials: E
authors.lastname: Van Den Berg
authors.forename: W M
authors.initials: WM
authors.lastname: Molenaar
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002648:Child; D003893:Desmin / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local; D012208:Rhabdomyosarcoma / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003893:Desmin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein