title: Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer.
abstract: BACKGROUND
  Decreased expression of the interferon-stimulated, putative tumour suppressor gene XAF1 has been shown to play a role during the onset, progression and treatment failure in various malignancies. However, little is yet known about its potential implication in the tumour biology of clear-cell renal cell cancer (ccRCC).
  
  
  METHODS
  This study assessed the expression of XAF1 protein in tumour tissue obtained from 291 ccRCC patients and 68 normal renal tissue samples, utilizing immunohistochemistry on a tissue-micro-array. XAF1 expression was correlated to clinico-pathological tumour features and prognosis.
  
  
  RESULTS
  Nuclear XAF1 expression was commonly detected in normal renal- (94.1%) and ccRCC (91.8%) samples, without significant differences of expression levels. Low XAF1 expression in ccRCC tissue, however, was associated with progression of tumour stage (p = 0.040) and grade (p < 0.001). Low XAF1 tumour levels were also prognostic of significantly shortened overall survival times in univariate analysis (p = 0.018), but did not provide independent prognostic information.
  
  
  CONCLUSIONS
  These data suggest down-regulation of XAF1 expression to be implicated in ccRCC progression and implies that its re-induction may provide a therapeutic approach. Although the prognostic value of XAF1 in ccRCC appears to be limited, its predictive value remains to be determined, especially in patients with metastatic disease undergoing novel combination therapies of targeted agents with Interferon-alpha.
authors: Institute of Surgical Pathology, UniversitätsSpital Zürich, 8091 Zurich, Switzerland. carsten.kempkensteffen@charite.de
authors: Carsten
authors: C
authors: Kempkensteffen
authors: Florian Rudolf
authors: FR
authors: Fritzsche
authors: Manfred
authors: M
authors: Johannsen
authors: Steffen
authors: S
authors: Weikert
authors: Stefan
authors: S
authors: Hinz
authors: Manfred
authors: M
authors: Dietel
authors: Marc-Oliver
authors: MO
authors: Riener
authors: Holger
authors: H
authors: Moch
authors: Klaus
authors: K
authors: Jung
authors: Hans
authors: H
authors: Krause
authors: Kurt
authors: K
authors: Miller
authors: Glen
authors: G
authors: Kristiansen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human