[1034] Tyrosine Kinase Inhibitor-Induced Vasculopathy in Clear Cell Renal Cell Carcinoma as an Anti-Tumor Mechanism

Toyonori Tsuzuki, Naoto Sassa, Takamitsu Morikawa, Akitoshi Fukatsu, Yasushi Yoshino, Ryohei Hattori, Ryouichi Shiroki, Momokazu Gotoh. Nagoya Daini Red Cross Hospital, Nagoya, Japan; Nagoya University, Nagoya, Japan; Fujita Health University, Toyoake, Japan; Komaki Municipal Hospital, Komaki, Japan

Background: Tyrosine kinase inhibitors (TKIs) are one of the first-line drugs for the treatment of unresectable or metastatic clear cell renal cell carcinoma (CCRCC). It is hypothesized that the mechanism underlying the anti-tumor effect of TKIs for CCRCC is inhibition of tumor neovascularization by blockade of the vascular endothelial growth factor receptor. However, the true mechanism underlying the anti-tumor effect of TKI is not fully explained.
Design: Nineteen patients were retrospectively administered TKI (sunitinib or sorafenib) for treatment of CCRCC. Sixteen of them underwent radical nephrectomy after neoadjuvant therapy with a TKI (sunitinib, 13; sorafenib, 3), and the remaining 3 died of the disease despite TKI administration (sunitinib, 2; sorafenib, 1), and their cadavers were subjected to an autopsy.
Results: The patient population was predominantly male (male to female ratio, 15:4). The mean patient age was 62 years (range, 27–76 years). Two types of regions were found in all the tumors: One characterized by necrosis and/or degeneration, which indicated anti-tumor activity, and the other by no or few pathological changes, which indicated absence of anti-tumor activity. The extent of degeneration and necrosis were varied across the different areas. Vasculopathy of tumor vessels was observed in or adjacent to the necrotic or degenerative area. Vasculopathy was of 2 types, defined by the following characteristics (1) concentric intimal thickening in medium-sized tumor vessels, which resulted in narrowing or occlusion of the lumen, or (2) by hyalinization in small-sized tumor vessels, which resulted in occlusion of the lumen. Little or no vasculopathy changes were observed in tumor vessels in areas affected by CCRCC, which indicated the absence of anti-tumor activity or low levels of activity.
Conclusions: This is the first report of vasculopathy in cases of TKI-treated CCRCC. Our data suggest that TKI induced vasculopathy in the tumor vessels initially, which resulted in anti-tumor activity characterized by ischemic changes. Our data also suggest that the anti-tumor effects of TKI in CCRCC treatment may be better evaluated by the extent and intensity of vasculopathy rather than the extent of necrosis or degenerative changes in the tumor.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 143, Tuesday Morning

 

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