Kempkensteffen Carsten, Fritzsche Florian Rudolf, Johannsen Manfred, Weikert Steffen, Hinz Stefan, Dietel Manfred, Riener Marc-Oliver, Moch Holger, Jung Klaus, Krause Hans, Miller Kurt, Kristiansen Glen
Institute of Surgical Pathology, UniversitätsSpital Zürich, 8091 Zurich, Switzerland.
BMC Cancer. 2009 Aug 8;9:276. doi: 10.1186/1471-2407-9-276.
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).
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.
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.
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.
干扰素刺激的假定肿瘤抑制基因XAF1的表达降低已被证明在多种恶性肿瘤的发生、发展和治疗失败过程中起作用。然而，关于其在透明细胞肾细胞癌（ccRCC）肿瘤生物学中的潜在影响，目前知之甚少。
本研究利用组织微阵列免疫组化技术，评估了291例ccRCC患者肿瘤组织和68例正常肾组织样本中XAF1蛋白的表达情况。XAF1表达与临床病理肿瘤特征及预后相关。
在正常肾组织（94.1%）和ccRCC组织（91.8%）样本中普遍检测到核XAF1表达，表达水平无显著差异。然而，ccRCC组织中XAF1低表达与肿瘤分期进展（p = 0.040）和分级（p < 0.001）相关。在单因素分析中，XAF1肿瘤低水平也预示着总生存时间显著缩短（p = 0.018），但未提供独立的预后信息。
这些数据表明XAF1表达下调与ccRCC进展有关，提示其重新诱导可能提供一种治疗方法。虽然XAF1在ccRCC中的预后价值似乎有限，但其预测价值仍有待确定，特别是在接受靶向药物与α干扰素联合新疗法的转移性疾病患者中。
