Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

Mod Pathol. 2012 Jan;25(1):100-11. doi: 10.1038/modpathol.2011.136. Epub 2011 Aug 26.


The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly α-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papain-like cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly used markers for their identification, especially to confirm the diagnosis on needle biopsies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Oxyphilic / enzymology
  • Angiomyolipoma / enzymology
  • Biomarkers, Tumor / analysis*
  • Case-Control Studies
  • Cathepsin K / analysis*
  • Humans
  • Immunohistochemistry
  • Italy
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / pathology
  • Lymphangioleiomyomatosis / enzymology
  • Perivascular Epithelioid Cell Neoplasms / enzymology*
  • Perivascular Epithelioid Cell Neoplasms / pathology


  • Biomarkers, Tumor
  • CTSK protein, human
  • Cathepsin K

Supplementary concepts

  • Oncocytoma, renal