[821] MiTF/TFE Family Renal Translocation Carcinomas Immunoexpress Cathepsin-K

G Martignoni, M Pea, S Gobbo, M Brunelli, F Bonetti, D Segala, C-C Pan, G Netto, C Doglioni, O Hes, P Argani, M Chilosi. Universit di Verona, Verona, Italy; Ospedale Orlandi, Bussolengo, Italy; Veterans General Hospital, Taipei, Taiwan; Johns Hopkins University, Baltimore; Istituto Scientifico San Raffaele, Milano, Italy; Charles University Hospital, Pilsen, Czech Republic

Background: MiTF/TFE family renal translocation carcinomas (tC) bear specific chromosome translocations that result in overexpression of TFE3 fusion gene products or native TFEB. TFE3 fusion gene product overexpression is due to different translocations involving chromosome Xp11.2 whereas TFEB overexpression is the result of the specific t(6;11). Both TFE3 and TFEB are closely related members of the MiTF/TFE transcription factor family which also includes TFEC and MiTF. All these transcription factors bind specific target DNA both as homodimers or heterodimers, and have overlapping transcriptional targets. Recently overexpression of MiTF has been related to the expression of cathepsin-K in osteoclasts. The aim of this study is to evaluate cathepsin-K immunoexpression in MiTF/TFE family renal tC and its usefulness in their differential diagnosis.
Design: We studied the immunohistochemical expression of cathepsin-K in 9 cytogenetically confirmed MiTF/TFE family tC. Three cases demonstrated a t(6;11), and 6 cases had translocations involving Xp11.2, two cases t(X;1) PRCC-TFE3; three cases t(X;1) PSF-TFE3 and one t(X;3). As control we analyzed the immunoexpression of cathepsin-K in 140 clear cell renal cell carcinomas (RCC), 20 papillary RCC, 8 chromophobe RCC and 8 oncocytomas.
Results: All TFEB tC showed strong and diffuse cytoplasmic labeling for cathepsin-K. Among the cytogenetically confirmed TFE3 tC, 3 out of 6 were positive (two PRCC-TFE3 and one PSF-TFE3 tC). None of the clear cell RCC, papillary RCC, chromophobe RCC or oncocytoma labelled for cathepsin-K.
Conclusions: 1) Cathepsin-K is consistently and strongly expressed in TFEB tCs. 2) Cathepsin-K is expressed in 50% of the TFE3 tCs. It is possible that whether or not there is expression may be related to the specific TFE3 fusion harbored by the neoplasm. 3) Cathepsin-K immunoexpression in both TFE3 and TFEB tCs distinguishes these neoplasms from the more common adult RCCs 4) These results suggest that overexpression of TFE3 fusion proteins or native TFEB in these renal neoplasms activates expression of genes normally regulated by MiTF in different cell types.
Category: Genitourinary (including renal tumors)

Monday, March 9, 2009 8:15 AM

Platform Session: Section A, Monday Morning