Cathepsin k: A novel diagnostic and predictive biomarker for renal tumors

Anna Caliò, Matteo Brunelli, Stefano Gobbo, Pedram Argani, Enrico Munari, George Netto, Guido Martignoni

Research output: Contribution to journalReview articlepeer-review


Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by os-teoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.

Original languageEnglish (US)
Article number2441
Issue number10
StatePublished - May 2 2021


  • Angiomyolipoma
  • Cathepsin K
  • Differential diagnosis
  • MTOR pathway
  • PEComa
  • Predictive markers
  • Renal cancers
  • TSC1/TSC2
  • Translocation renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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