Caliò Anna, Brunelli Matteo, Gobbo Stefano, Argani Pedram, Munari Enrico, Netto George, Martignoni Guido
Department of Diagnostic and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy.
Department of Pathology, Pederzoli Hospital, 37019 Peschiera del Garda, Italy.
Cancers (Basel). 2021 May 18;13(10):2441. doi: 10.3390/cancers13102441.
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 osteoclasts. 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 gene mutations. Interestingly, both mutations or 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.
组织蛋白酶K是一种具有高基质降解活性的木瓜蛋白酶样半胱氨酸蛋白酶。在几种组织蛋白酶中，组织蛋白酶K是最有效的哺乳动物胶原酶，主要由破骨细胞表达。本综述总结了组织蛋白酶K表达的最新研究结果，强调了其在肾肿瘤诊断中的作用以及作为潜在分子靶点的作用。事实上，组织蛋白酶K是识别TFE3/TFEB重排肾细胞癌、TFEB扩增肾细胞癌和纯上皮样PEComa/上皮样血管平滑肌脂肪瘤的公认诊断工具。最近，在一组以基因突变分子特征为特点的嗜酸性肾肿瘤中观察到了它的表达。有趣的是，在纯上皮样PEComa/上皮样血管平滑肌脂肪瘤中都报道了 突变或重排。因此，组织蛋白酶K似乎是TFE3/TFEB重排、TFEB扩增和mTOR通路激活的下游标志物。鉴于mTOR抑制剂在肾癌中作为一种药理学选择的既定作用，组织蛋白酶K可用作治疗反应的预测标志物和潜在靶点。未来，泌尿病理学家可能会使用组织蛋白酶K来对具有透明细胞、乳头结构和嗜酸性特征的肾肿瘤进行诊断。
