616 CHARACTERISTICS OF PRIMARY TUMOR MAY PREDICT BONE METASTASIS IN RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: The poor prognosis of renal cell carcinoma (RCC) is caused by a high risk of metastasis. 30% of RCC patients develop bone metastases during the course of disease. A method of predicting bone metastasis would benefit the otherwise poor outcome of this patient group. The aim of this study was to elucidate the mechanisms that lead to organ-specific metastasis of RCC in bones and thereby predict bone metastasis. METHODS: In 30 RCC tissue specimens and 9 RCC primary cell lines collected from patients who had developed no metastases, lung or bone metastases within 5 years after nephrectomy (each 10 RCC tissue specimens, each 3 RCC cell lines) expression and/or activity of 46 cellular signaling molecules were quantified by phosphokinase array and Western blot analyses. To investigate metastatic behavior, migration of the primary RCC cells was analysed in a Boyden chamber with 10 g/ml fibronectin as chemotaxin, and adhesion to extracellular matrix compounds fibronectin, collagen I and IV was determined after cell staining with crystal violet. RESULTS: In RCC tissue specimens and primary cells from patients who developed bone metastases, a higher expression of 5 integrins, higher activity of Akt and FAK and a lower expression of PTEN were detected, compared to those from patients without or with lung metastases. These results show an enhanced chemotactic migration (13-fold) of bone metastatic RCC cells and adhesion to fibronectin (6-fold) or collagen type I (8-fold) both components of the bone matrix. CONCLUSIONS: Specific characteristics such as expression and activity of cell signaling mediators and cellular behavior of the primary tumor determine the location of subsequent metastasis in RCC and could be used as a prognostic marker for bone metastasis. This should be considered during follow-up care.