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), MRPI, 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, MRPI, 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% (MRPI), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRPI associated, respectively, to low AFP (P = 0.026) and high LDH levels (P = 0.014), whereas LRP expression associated with high β-hCG levels (P = 0.003) and stage IV tumours (P = 0.029). No correlation was found between Pgp, MRPI, 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. © 2003 Cancer Research UK.