Quantitative comparison of erythropoietin receptor levels in the epithelial versus endothelial fractions of primary breast tumors.

ABSTRACT

BACKGROUND: Erythropoietin (EPO) was shown to reduce tumor survival in recent trials, however, its mechanisms of action are unclear. Efforts to measure tumor EPO receptor (EPOR) are limited by the promiscuity of EPOR antibodies, and concerns as to whether EPOR mRNA measurements are confounded by heterogeneity of tumor vasculature, a known EPOR source. MATERIALS AND METHODS: This study compared mRNA levels of EPOR and JAK2 in 11 breast tumor epithelial versus endothelial dissections. RESULTS: In nine tumors EPOR mRNA was 2.6 (1.2-5.7)-fold lower in the epithelial fraction, however, this reduction was less than the reduction of endothelial markers. In two tumors, EPOR mRNA was 2.9 (1.7-4.0)-fold higher in the epithelial fraction. The inter-tumor variation in EPOR levels exceeded the intra-tumor variation between fractions. Similar results were obtained for JAK2. CONCLUSION: Tumor vasculature is not the sole source of EPOR and JAK2, and tumors can be segregated by EPOR and JAK2 levels for correlative analysis with clinical outcomes.