Prognostic Value of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) and TRAIL Receptors in Renal Cell Cancer

• Published in: Clinical cancer research 2009-01, Vol.15 (2), p.650-659
• Main Authors: MACHER-GOEPPINGER, Stephan, AULMANN, Sebastian, TEH, Bin T, AUTSCHBACH, Frank, HERPEL, Esther, SCHIRMACHER, Peter, ROTH, Wilfried, TAGSCHERER, Katrin E, WAGENER, Nina, HAFERKAMP, Axel, PENZEL, Roland, BRAUCKHOFF, Antje, HOHENFELLNER, Markus, SYKORA, Jaromir, WALCZAK, Henning
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic agents; apoptosis; Biological and medical sciences; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - metabolism; death receptors; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms - diagnosis; Kidney Neoplasms - metabolism; Kidneys; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Prognosis; Proportional Hazards Models; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; renal cell cancer; TNF-Related Apoptosis-Inducing Ligand - metabolism; TRAIL; Treatment Outcome; Tumors of the urinary system
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0284

Purpose: The death ligand tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R) are involved in immune surveillance and tumor development. Here, we studied a possible association between the expression of TRAIL/TRAIL-Rs and the prognosis in patients with renal cell carcinomas (RCC). Experimental Design: A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples from 838 patients was generated. Expression of TRAIL and TRAIL-Rs was examined by immunohistochemistry and the effect of TRAIL and TRAIL-R expression on disease-specific survival was assessed. Results: High TRAIL-R2 expression levels were associated with high-grade RCCs ( P < 0.001) and correlated negatively with disease-specific survival ( P = 0.01). Similarly, high TRAIL expression was associated with a shorter disease-specific survival ( P = 0.01). In contrast, low TRAIL-R4 expression was associated with high-stage RCCs ( P < 0.001) as well as with the incidence of distant metastasis ( P = 0.03) and correlated negatively with disease-specific survival ( P = 0.02). In patients without distant metastasis, multivariate Cox regression analyses revealed that TRAIL-R2 and TRAIL are independent prognostic factors for cancer-specific survival (in addition to tumor extent, regional lymph node metastasis, grade of malignancy, and type of surgery). Conclusion: High TRAIL-R2, high TRAIL, and low TRAIL-R4 expression levels are associated with a worse disease-specific survival in patients with RCCs. Therefore, the assessment of TRAIL/TRAIL-R expression offers valuable prognostic information that could be used to select patients for adjuvant therapy studies. Moreover, our findings are of relevance for a potential experimental therapeutic administration of TRAIL-R agonists in patients with RCCs.