Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney
Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney
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DOI：
10.1038/modpathol.2011.136
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发表时间：
2012-01-01
期刊：
影响因子：
7.5
通讯作者：
Pea, Maurizio
中科院分区：
文献类型：
--
作者：
Martignoni, Guido;Bonetti, Franco;Pea, Maurizio
血管周围上皮样细胞(PEC)是一种独特的细胞类型，共表达收缩蛋白(主要是α-平滑肌肌动蛋白)、黑素细胞标志物，包括小眼球相关转录因子(MITF)和雌孕激素受体。它经常出现在一组名为PEComas的肿瘤中。肾内膜脂肪瘤包括常见的血管肌脂肪瘤，也包括少见的病变，如显微镜下的血管肌脂肪瘤、肾小球内病变、伴上皮囊肿的血管肌脂肪瘤、上皮样血管肌脂肪瘤、嗜酸细胞瘤样血管肌脂肪瘤和肾窦淋巴管肌瘤病。已经证明，这些损害中的大多数是由影响结节性硬化症复合体、结节性硬化症1(TSC1)和结节性硬化症2(TSC2)的基因突变决定的，最终导致Rheb/MTOR/RPS6KB2通路的调节解除，并观察到一些PEComa在MTOR抑制剂西罗莫司治疗期间退化。最近，MITF的过度表达与其抑制MTOR的破骨细胞中木瓜蛋白酶样半胱氨酸蛋白酶组织蛋白K的表达有关。这项研究的目的是用免疫组织化学方法评估组织蛋白酶K在肾脏PEComa病变的整个谱系中的作用。研究对象包括84个肾脏PEComa病变，其中5个以脂肪为主(脂肪瘤样血管平滑肌脂肪瘤)，15个几乎全部由梭形平滑肌细胞组成(平滑肌瘤样血管脂肪瘤)，31个常见的由脂肪、梭形和上皮样平滑肌细胞和异常厚壁血管组成的血管平滑肌脂肪瘤，15个显微镜下的血管平滑肌脂肪瘤，5个肾小球内病变，2个瘤细胞瘤样血管肌脂肪瘤，8个上皮样血管平滑肌脂肪瘤，2个伴上皮样囊肿的血管平滑肌脂肪瘤和1例肾窦淋巴管肌瘤病。在所有的肾脏PEComa中，组织蛋白酶K都有持续和强烈的表达，似乎是一种比其他常用的标志物更有效的标记物，尤其是在确认针吸活检的诊断方面。《现代病理学》(2012年)25100111；doi：10.1038/modpathol.2011.136；2011年8月26日在线发布
The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly alpha-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. Modern Pathology (2012) 25, 100-111; doi:10.1038/modpathol.2011.136; published online 26 August 2011