[820] Cathepsin-K Expression in Both Classic and Epithelioid Angiomyolipoma of the Kidney

G Martignoni, F Bonetti, M Chilosi, M Brunelli, M Amin, JN Eble, S Gobbo, M Pea. Universit di Verona, Verona, Italy; Cedars-Sinai Medical Center, Los Angeles; Indiana University, Indianapolis; Ospedale Orlandi, Bussolengo, Italy

Background: Angiomyolipoma is the most common mesenchymal tumor of the kidney. It can occur in patients with and without tuberous sclerosis, an inherited syndrome due to losses of TSC1 or TSC2 genes having an important role in the regulation of mTOR pathway which is suppressed by Sirolimus and analogous drugs. Epithelioid angiomyolipoma is a variant of angiomyolipoma composed of cells which closely resemble high grade or sarcomatoid renal cell carcinoma. Unlike classic angiomyolipoma, it can recur locally, metastasize, and cause death. Both the usual angiomyolipoma and epithelioid angiomyolipoma are frequently coexpress myogenic (actin) and melanocytic markers including MiTF. Recently overexpression of MiTF has been related to the expression of the papain-like cysteine protease cathepsin-K in osteoclasts where it has been inhibited by the mTOR inhibitor Everolimus. The aim of this study is to evaluate cathepsin-K immunoexpression in usual and epithelioid angiomyolipomas.
Design: We studied the immunoexpression of cathepsin-K in 20 usual and 4 epithelioid angiomyolipomas occurring in patients with (3) and without (21) tuberous sclerosis. As controls we analyzed the immunoexpression of cathepsin-K also in 140 clear cell renal cell carcinomas, 20 papillary renal cell carcinomas, 8 chromophobe renal cell carcinomas and 8 renal oncocytomas.
Results: In all of the usual renal angiomyolipomas strong cathepsin-K expression was demonstrated both in adipocyte-like cells and in smooth muscle cells. Similarly, all of the epithelioid angimyolipomas showed a strong and diffuse positive reaction with antibody to cathepsin-K. None of the clear cell renal cell carcinomas, papillary renal cell carcinomas, chromophobe renal cell carcinomas or renal oncocytomas showed a positive reaction with antibody to cathepsin-K.
Conclusions: We demonstrated that: 1) cathepsin-K is constantly and strongly expressed in both usual and epithelioid angiomyolipomas and can be a robust marker for their identification; 2) the expression in epithelioid angiomyolipoma of cathepsin-K, which has been demonstrated to be modulated by mTOR inhibitors such as Sirolimus, may suggest a rational base to test these drugs in patients with these tumors.
Category: Genitourinary (including renal tumors)

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 133, Wednesday Afternoon