Evaluation of the KIT/Stem Cell Factor Axis in Renal Tumours

Aim: To investigate the expression of the KIT/stem cell factor (SCF) axis in different renal cell carcinoma subtypes with regard to targeted therapies. Materials and Methods: The expression of KIT and SCF were immunhistochemically assessed in 40 clear cell (ccRCC), 25 papillary (pRCC) and 19 chromophobe carcinomas (chRCC); 27 oncocytomas and 32 benign kidney parenchyma specimens differentiated into distal tubules (DT) and proximal tubules (PT). Results: The expression of KIT was significantly higher in chRCC and oncocytoma compared to ccRCC and pRCC. All tumours exhibited a significant increase of membranous to cytoplasmic KIT expression, with the highest in ccRCC and pRCCs. SCF was expressed in all tumour subgroups, with the highest in oncocytomas and pRCC. SCF correlated positively with the cytoplasmic expression of KIT. A higher tumour stage correlated to lower KIT expression in ccRCC. Conclusion: Simultaneous expression of SCF and KIT in renal tumours, which seems to undergo a shift from the cytoplasm to the cell membrane, suggests paracrine and autocrine mechanisms in KIT activation, with different, as yet unknown, regulatory mechanisms in the different tumour entities. Renal cell cancer (RCC) is the seventh most common malignancy in men and the ninth in women. In Europe an estimated 88,400 new patients were diagnosed with this disease in 2008 (1). In comparison to other urological malignancies, renal cell cancer represents the tumour entity, with the highest death rate. During the past decades, knowledge on molecular biology of renal tumours has increased tremendously. This has led to the development of several new targeted therapies that have opened-up a new era of treatment for patients with metastasized disease. One of the targets addressed but rarely described is KIT, also known as c-Kit or CD 117 (cluster of differentiation 117) which is a 145-150 kDa glycoprotein encoded by the KIT gene that is localized on chromosome 4 (4q11-q21). KIT is a