Expression and Prognostic Value of the Lung Resistance-related Protein (LRP) in Germ Cell Testicular Tumors

Background: Lung resistance-related protein (LRP) was first detected in a non-P-glycoprotein-mediated multidrug- resistant lung cancer cell line and has been shown to be the major human vault protein. The aim of this study was to evaluate the expression of LRP in germ cell testicular tumors (GCT) and to determine the correlation between LRP expression and the clinical outcome of these tumors. Patients and Methods: Seventy cases of primary testicular tumors were investigated. LRP protein was detected by immuno- histochemistry and Western blotting methods. LRP mRNA was determined with RT-PCR. Patients' clinical parameters and tumor response to treatment were recorded. Results: With immunohistochemistry, LRP was detected in 29 (41%) out of 70 primary testicular tumors. Twenty-two (63%) out of 35 tumors expressed LRP mRNA and LRP protein on examination by RT-PCR and Western blotting, respectively. Pure teratomas showed significantly higher LRP expression compared to other types of GCTs (p=0.0418). No relationship was demonstrated between the LRP immunostaining and stage of disease (p=0.2263). A significantly higher proportion of patients with LRP-negative tumors achieved complete response than those with LRP-positive tumors (p=0.0155). Patients whose tumors showed expression of LRP had significantly shorter overall survival (p=0.0428) than LRP-negative patients. Conclusion: Immunohistochemistry is a reliable method to evaluate LRP expression in testicular germ cell tumors. A positive correlation was found between LRP immunostaining and pure teratomas. LRP expression was associated with an adverse clinical outcome and shorter overall survival. Our findings suggest that LRP has prognostic value in testicular germ cell tumors and can predict clinical outcome. Testicular tumors account for 1-2% of all male malignancies. Over 95% of these cancers are germ cell tumors (GCT); seminoma and non-seminomatous germ cell tumor (NSGCT) each account for approximately half of testicular cancer cases. GCTs are one of the most sensitive cancers to cytostatic therapy, since in disseminated cases a remission rate of approximately 80% can be achieved with cisplatin- based combined chemotherapy. Resection of radiologically detected residual tumor after chemotherapy may further increase the cure rate. Despite good results with multimodality treatment, some patients ultimately die of their disease due to tumor resistance