FAPα and αSMA mark different subsets of fibroblasts in normal kidney and conventional renal cell carcinoma

Several studies suggested a correlation between cancer associated fibroblasts (CAF) and cancer progression, but data on conventional renal cell carcinoma (cRCC) is still lacking. We aimed to analyse the impact of αSMA positive myo-CAF and FAPα expressing i-CAF on postoperative relapse of cRCC. We applied immunohistochemistry on tissue-multiarray (TMA) containing 736 consecutively operated cRCC without metastasis at the time of diagnosis. We analysed the correlation between the amount and pattern of αSMA and FAPα expressing CAFs and tumour cells and postoperative tumour relapse. Stromal fibroblasts of each cRCC displayed αSMA immunreaction but only 142 of the 736 tumours showed positive FAPα staining. There was no correlation between the amount of αSMA and or FAPα positive CAFs and tumour progression. However, tumours with large tourtous vessels with strong αSMA positive immunreaction have more then two times higher risk of postoperative tumour relapse (RR=2.198, p = 0.005). Patients with cRCC (57) showing cytoplasmic αSMA staining of tumour cells had a nearly two times higher risk for postoperative progression (RR=1.776, p = 0.014). There is no significant correlation between the density of αSMA or FAPα positive CAFs and postoperative relapse of cRCCs, therefore CAFs in cRCC are not suitable targets for therapy. Further limitation of anti-CAF therapy of cRCC that stromal cells of normal kidney are positive with αSMA antibody.