title: Expression parameters of the inhibitors of apoptosis cIAP1 and cIAP2 in renal cell carcinomas and their prognostic relevance.
abstract: The expression of the inhibitor of apoptosis (IAP) family members cIAP1 and cIAP2 have been shown to be altered in various cancer entities. This study was done to characterize the tumor-related expression profile of cIAP1 and cIAP2 in patients with renal cell carcinomas (RCC) and to evaluate its potential predictive value after curative resection. Expression of cIAP1 and cIAP2 was analyzed by real-time RT-PCR in RCC and corresponding normal tissue samples obtained from a cohort of 127 RCC patients (median follow-up: 48 months) undergoing surgical treatment. Expression data was correlated to histopathological variables and outcome. Overexpression of cIAP1 and cIAP2 occurred in most RCC specimens (p < 0.001), but 20% of the patients had lower cIAP levels in malignant than in normal tissue. The cIAP1 expression correlated with the tumor stage, levels being higher in pT1 tumors than in advanced pathological stages (p = 0.002). Decreased cIAP1 expression in RCC relative to paired normal samples predicted an abbreviated time to recurrence (hazard rate 2.96; 95% CI: 1.23-7.09) and tumor-specific survival (hazard rate 2.78; 95% CI: 1.22-6.38) irrespective of the tumor stage and grade. The prognostic effect of cIAP1 was most pronounced in patients with pT3 disease (log rank test p = 0.001). The results of uni- and multivariate analysis suggest a prognostic value of cIAP1 expression for RCC patients, downregulation indicating an aggressive, potentially lethal phenotype.
authors.affiliation: Department of Urology, Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany. carsten.kempkensteffen@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinz
authors.forename: Frank
authors.initials: F
authors.lastname: Christoph
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases
chemical_list: D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; C494833:BIRC2 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases