title: Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.
abstract: 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.
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Franco
authors.initials: F
authors.lastname: Bonetti
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Diego
authors.initials: D
authors.lastname: Segala
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Stefano
authors.initials: S
authors.lastname: Gobbo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pea
mesh_terms: D018249:Adenoma, Oxyphilic / Q000201:enzymology; D018207:Angiomyolipoma / Q000201:enzymology; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D056657:Cathepsin K / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000201:enzymology; D054973:Perivascular Epithelioid Cell Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C534130:CTSK protein, human; D056657:Cathepsin K