Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation
Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation
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DOI：
10.1016/j.humpath.2012.10.001
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发表时间：
2013-06-01
期刊：
影响因子：
3.3
通讯作者：
Zhang, Paul J.
中科院分区：
文献类型：
--
作者：
Dickson, Brendan C.;Riddle, Nicole D.;Zhang, Paul J.
Sirtuin，沉默交配型信息调节2同源物酿酒酵母1（SIRT 1），是一种涉及多种哺乳动物功能的蛋白质，包括细胞衰老，抗应激和分化。SIRT 1还被证明与多种肿瘤有关。此外，靶向SIRT 1的新药物疗法最近已被批准。本研究的目的是利用免疫组织化学方法来表征SIRT 1蛋白在人类软组织肿瘤中的表达，以期找到新的诊断和治疗方法。回顾了164例软组织肿瘤的SIRT 1免疫反应，包括腺泡状软组织肉瘤、血管平滑肌脂肪瘤、透明细胞肉瘤、硬纤维瘤/纤维瘤病、促纤维增生性小圆细胞瘤、尤文肉瘤、胃肠道间质瘤、血管球瘤、平滑肌瘤、平滑肌肉瘤、脂肪瘤、脂肪肉瘤、恶性外周神经鞘瘤、结节性筋膜炎、骨肉瘤、横纹肌肉瘤、神经鞘瘤、孤立性纤维瘤、滑膜肉瘤、未分化多形性肉瘤和肾母细胞瘤。此外，测试了许多良性组织的SlRT 1反应性。在非肿瘤组织中，在所有前列腺造口、平滑肌和横纹肌中观察到强的细胞质SIRT 1反应。在具有肌样分化的软组织肿瘤中观察到类似的胞质SIRT 1表达模式，即血管平滑肌脂肪瘤（100%）、血管球瘤（100%）、平滑肌瘤（90%）、平滑肌肉瘤（76.5%）和横纹肌肉瘤（87%）。检查的其他病变均为阴性。尽管SIRT 1在肌样组织和肿瘤分化沿着这些线中的生理作用仍有待澄清，但这一观察结果指出了该标记物在诊断免疫组织化学中的潜在作用。此外，最近出现的能够选择性抑制SIRT 1的药物提高了靶向治疗的可能性。需要进一步研究SIRT 1在肌样组织和肿瘤中的作用。(C)2013 Elsevier Inc. All rights reserved.
Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1. The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities. SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor. In addition, numerous benign tissues were tested for SlRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stoma, smooth muscle, and striated muscle. A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76.5%), and rhabdomyosarcoma (87%). The other lesions examined were negative. Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry. Furthemore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy. Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms. (C) 2013 Elsevier Inc. All rights reserved.