title: Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours.
abstract: This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.
authors.affiliation: Department of Medical Oncology and Laboratory of Translational Research, Institut Català d'Oncologia, Barcelona, Spain.
authors.forename: A J
authors.initials: AJ
authors.lastname: Zurita
authors.forename: J E
authors.initials: JE
authors.lastname: Diestra
authors.forename: E
authors.initials: E
authors.lastname: Condom
authors.forename: X
authors.initials: X
authors.lastname: García Del Muro
authors.forename: G L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: J
authors.initials: J
authors.lastname: Pérez
authors.forename: J R
authors.initials: JR
authors.lastname: Germà-Lluch
authors.forename: M A
authors.initials: MA
authors.lastname: Izquierdo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D009919:Orchiectomy; D011379:Prognosis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002945:Cisplatin; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein