Differential expression of potassium ion channels in human renal cell carcinoma

Purpose  Ether-a-go-go (EAG) or EAG-related (ERG) voltage-gated potassium ion channels are involved in tumor generation and progression. Their over- and/or misexpression has been demonstrated in various tumors, and inhibition of these channels has suppressed proliferation of various cancer cells. We investigate and compare the pattern of expression of EAG and human ERG (HERG) channels in renal cell carcinoma and “normal” renal tissue. Method  Tissue samples, obtained at the time of radical nephrectomy from the tumor-bearing areas, and uninvolved renal tissue were preserved in 4% paraformaldehyde and cryosectioned at 20 μm. Immunohistochemical and Western blot analysis was performed on the tumor and uninvolved kidney parenchyma by incubating with polyclonal anti-HERG 1b (Alomone Lab, Israel), anti-EAG1, and anti-EAG2. Pattern of expression of EAG/HERG channels in normal renal tissue and carcinoma were noted and compared. Results  The study was performed on 16 radical and four partial nephrectomy specimens (n = 20). All tumors in the cohort were clear cell renal carcinoma. Normal renal tissue was found to exhibit heterogeneous cytoplasmic positivity for EAG1 and focal HERG immunoreactivity (IR) in the proximal (PCT) and distal convoluted tubules (DCT). EAG2 IR was absent in the normal renal tissue. Clear cell RCC demonstrated a loss of HERG expression while diffuse overexpression of EAG1 and EAG2 was noted. Western blot analysis corroborated the immunohistochemical observations. Conclusions  In our study both EAG1 and EAG2 potassium channels were overexpressed in clear cell renal cancer. In contrast to other adenocarcinomas, there is loss of HERG expression in clear cell RCC, which may possibly explain its chemoresistance. These ion channels may provide a potential for targeted therapy.