1. ¹Department of Medical Oncology and Laboratory of Translational Research, Institut Català d'Oncologia, Av Gran Via Km 2.7, 08907 Barcelona, Spain
2. ²Department of Pathology, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga s/n, 08907 Barcelona, Spain
3. ³Department of Pathology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands

Correspondence: Dr MA Izquierdo, Department of Medical Oncology, Institut Català d'Oncologia, Av. Gran Via, Km 2.7, Hospitalet de Llobregat, 08907 Barcelona, Spain. E-mail: maizquierdo.delso@csub.scs.es

⁴Current address: Department of Genito-Urinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

Received 2 October 2002; Revised 12 December 2002; Accepted 12 December 2002.

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 -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.