title: Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513,  Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Yoshii
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Akio
authors.initials: A
authors.lastname: Horiguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sumitomo
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano