Tissue expression and plasma levels of adrenomedullin in renal cancer patients

The peptide AM (adrenomedullin) is stimulated by hypoxia through HIF-1 (hypoxia-inducible factor-1). The majority of human CC-RCCs (clear cell renal cell carcinomas) display mutations in the tumour suppressor protein von Hippel–Lindau, which leads to constitutively elevated HIF-1. We hypothesized that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3–6 days after surgery and 4–5 weeks after surgery. AM mRNA and peptide expression in tissue and AM plasma concentration were determined. HIF-1α was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared with adjacent renal cortex (6-fold, n=18; P<0.02). There was no difference in AM mRNA between cortex and non-CC-RCC tissue (n=7). AM peptide concentration was elevated in CC-RCC tissue compared with adjacent cortex (4-fold, n=6; P<0.02), whereas there was no difference between cortex and non-CC-RCC tissue (n=5). HIF-1α immunoreactivity was detected in the majority of cell nuclei in 76% of CC-RCC, consistent with constitutive stabilization. In non-CC-RCC, HIF-1α staining was focal. Before surgery there was no difference in plasma AM concentration between tumour types. Nephrectomy increased plasma AM significantly after 3–6 days and a similar pre-surgery level was observed after 4–5 weeks in both groups of tumour patients. We conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease.