Tissue expression and plasma levels of adrenomedullin in renal cancer patients

Jens Michelsen , Helle C Thiesson , Steen Walter , Peter D Ottosen , Ole Skøtt , Boye L Jensen (1)

1 SDU - University of Southern Denmark

The peptide adrenomedullin (AM) is stimulated by hypoxia through Hypoxia Inducible Factor 1 (HIF-1). The majority of human clear cell renal cell cancers (CC-RCC) 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 and 4-5 weeks after surgery. We determined AM mRNA and peptide expression in tissue and AM plasma concentration. HIF-1{alpha} was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared to 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 to adjacent cortex (4-fold, n=6, P<0.02), while there was no difference between cortex and non-CC-RCC tissue (n=5). HIF-1{alpha} immunoreactivity was detected in the majority of cell nuclei in 76% of CC-RCC compatible with constitutive stabilization. In non-CC-RCC, HIF-1{alpha} 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 similar presurgery level was observed after 4-5 weeks in both groups of tumor patients. We conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared to other kidney tumours. Plasma AM is not suited as a tumour marker for this disease.

Mots clés: Medicine

Jens Michelsen, Helle C Thiesson, Steen Walter, Peter D Ottosen, Ole Skøtt, et al.. Tissue expression and plasma levels of adrenomedullin in renal cancer patients. Clinical Science, 2006, 111 (1), pp.61-70. ⟨10.1042/CS20060030⟩. ⟨hal-00479320⟩