Ito Keiichi, Yoshii Hidehiko, Asano Takako, Horiguchi Akio, Sumitomo Makoto, Hayakawa Masamichi, Asano Tomohiko
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
Exp Ther Med. 2012 Jun;3(6):937-944. doi: 10.3892/etm.2012.513. Epub 2012 Mar 13.
Erythropoietin (EPO) expression and EPO receptor (EpoR) expression have been demonstrated in various malignant tumors. EPO-EpoR signaling can activate several downstream signal transduction pathways that enhance tumor aggressiveness. The present study was undertaken to evaluate the impact of overexpression of EpoR and elevated serum EPO (sEPO) levels on the clinicopathological features and prognosis of patients with renal cell carcinoma (RCC). EpoR expression was evaluated immunohistochemically in 56 patients. Tumors with a staining intensity greater than that of surrounding proximal tubules were defined as tumors with high EpoR expression. The association between EpoR expression levels and various clinicopathological factors was analyzed. sEPO levels were determined in 138 patients and its correlation to clinicopathological factors was also analyzed, and EpoR expression was determined in surgical specimens removed from 47 of those 138 patients. Patients with high EpoR expression and patients with sEPO elevation had clinicopathological features less favorable than those of other patients. Tumors demonstrating high EpoR expression had a significantly higher number of Ki-67-positive cells compared to those with low EpoR expression. Tumor assemblies in microvessels demonstrated high EpoR expression. Patients whose tumors demonstrated high EpoR expression and those with sEPO elevation had a significantly lower survival rate compared to other patients, and patients with both high EpoR expression and sEPO elevation had an extremely poor prognosis. Microvascular invasion was an independent factor associated with sEPO elevation, suggesting that EPO-EpoR signaling might be important in RCC metastasis. EPO-EpoR signaling may be involved in tumor growth and progression in RCC and the combination of EpoR expression and sEPO levels may effectively predict clinical outcome.
促红细胞生成素（EPO）表达和促红细胞生成素受体（EpoR）表达已在多种恶性肿瘤中得到证实。EPO-EpoR信号传导可激活多种下游信号转导通路，增强肿瘤侵袭性。本研究旨在评估EpoR过表达和血清EPO（sEPO）水平升高对肾细胞癌（RCC）患者临床病理特征和预后的影响。采用免疫组织化学方法对56例患者的EpoR表达进行评估。染色强度大于周围近端小管的肿瘤被定义为EpoR高表达肿瘤。分析EpoR表达水平与各种临床病理因素之间的关联。测定了138例患者的sEPO水平，并分析其与临床病理因素的相关性，同时对其中47例患者手术切除标本中的EpoR表达进行了测定。EpoR高表达患者和sEPO升高患者的临床病理特征比其他患者差。与EpoR低表达的肿瘤相比，EpoR高表达的肿瘤中Ki-67阳性细胞数量显著更多。微血管中的肿瘤组织显示EpoR高表达。肿瘤EpoR高表达患者和sEPO升高患者的生存率显著低于其他患者，而EpoR高表达且sEPO升高的患者预后极差。微血管侵犯是与sEPO升高相关的独立因素，提示EPO-EpoR信号传导可能在RCC转移中起重要作用。EPO-EpoR信号传导可能参与RCC的肿瘤生长和进展，EpoR表达和sEPO水平的联合检测可能有效预测临床结局。
