Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer.
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.
Kempkensteffen
Carsten
C
Institute of Surgical Pathology, UniversitätsSpital Zürich, 8091 Zurich, Switzerland. carsten.kempkensteffen@charite.de
Fritzsche
Florian Rudolf
FR
Johannsen
Manfred
M
Weikert
Steffen
S
Hinz
Stefan
S
Dietel
Manfred
M
Riener
Marc-Oliver
MO
Moch
Holger
H
Jung
Klaus
K
Krause
Hans
H
Miller
Kurt
K
Kristiansen
Glen
G
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
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human