Cathepsin K is a lysosomal papain–like cystine proteinase and can be expressed in normal osteoblasts, fibroblasts, and skin.1 Recently, cathepsin K has been reported as useful in distinguishing translocation renal cell carcinoma (RCC) from other subtypes of RCC.¹ Mortignoni et al. tested 17 cases of translocation RCC and found that cathepsin K stained 6 of 8 cases of translocation RCC with t(X;1), all seven cases of translocation RCC with t(6;11), but was negative for one case with t(X;3) and one with t(X;17).1 Additionally, the study compared IHC detection of TFE3 antibody in the 17 cases and demonstrated that all translocation RCC with t(6;11) were completely negative for TFE3, but positive for cathepsin K; all other translocation RCC with different chromosomal tranlocations other than t(X;1) expressed TFE3.¹ Thus, it is recommended that antibodies against both TFE3 and cathepsin K should be used for evaluating translocation renal cell carcinomas.¹ None of the 305 other renal cell neoplasms representing the most common renal cell neoplasm subtypes were positive for cathepsin K.1 Zheng et al. reported only 2.7% of 1,140 carcinomas from various organs exhibited cathepsin K labeling, indicating that among carcinomas cathepsin K labeling is highly specific for translocation RCC and can be used to help differentiate translocation RCC from other carcinomas.²

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