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    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; IN-VITRO ; SURVIVAL ; tumor ; carcinoma ; CELL ; Germany ; THERAPY ; DEATH ; microarray ; SAMPLES ; MONOCLONAL-ANTIBODY ; SURGERY ; PATIENT ; NF-KAPPA-B ; LIGAND ; prognosis ; ASSOCIATION ; immunohistochemistry ; METASTASIS ; PROGNOSTIC-FACTORS ; CARCINOMA-CELLS ; TRAIL ; DEATH RECEPTORS ; CYTOTOXICITY ; APOPTOSIS-INDUCING LIGAND ; THERAPIES ; MEDIATED APOPTOSIS ; ENHANCEMENT ; development ; therapeutic ; DEATH LIGAND
    Abstract: 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
    Type of Publication: Journal article published
    PubMed ID: 19147771
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