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

Guido Martignoni, Franco Bonetti, Marco Chilosi, Matteo Brunelli, Diego Segala, Mahul B. Amin, Pedram Argani, John N. Eble, Stefano Gobbo, Maurizio Pea

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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.

Original languageEnglish (US)
Pages (from-to)100-111
Number of pages12
JournalModern Pathology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2012

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Cathepsin K
Angiomyolipoma
Epithelioid Cells
Perivascular Epithelioid Cell Neoplasms
Kidney
Microphthalmia-Associated Transcription Factor
Lymphangioleiomyomatosis
Oxyphilic Adenoma
Smooth Muscle Myocytes
Cysts
Fats
Contractile Proteins
Endopeptidase K
Tuberous Sclerosis
Papain
Cysteine Proteases
Lipoma
Leiomyoma
Needle Biopsy
Osteoclasts

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. / Martignoni, Guido; Bonetti, Franco; Chilosi, Marco; Brunelli, Matteo; Segala, Diego; Amin, Mahul B.; Argani, Pedram; Eble, John N.; Gobbo, Stefano; Pea, Maurizio.

In: Modern Pathology, Vol. 25, No. 1, 01.01.2012, p. 100-111.

Research output: Contribution to journalArticle

Martignoni, G, Bonetti, F, Chilosi, M, Brunelli, M, Segala, D, Amin, MB, Argani, P, Eble, JN, Gobbo, S & Pea, M 2012, 'Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney', Modern Pathology, vol. 25, no. 1, pp. 100-111. https://doi.org/10.1038/modpathol.2011.136
Martignoni, Guido ; Bonetti, Franco ; Chilosi, Marco ; Brunelli, Matteo ; Segala, Diego ; Amin, Mahul B. ; Argani, Pedram ; Eble, John N. ; Gobbo, Stefano ; Pea, Maurizio. / Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. In: Modern Pathology. 2012 ; Vol. 25, No. 1. pp. 100-111.
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