Department of Pathology, University of Toronto, Ontario, Canada M5S 1A8.
Hum Pathol. 2013 Jun;44(6):1125-30. doi: 10.1016/j.humpath.2012.10.001. Epub 2013 Jan 15.
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 SIRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, 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. Furthermore, 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.
Sirtuin，沉默交配型信息调节 2 同源物酿酒酵母 1（SIRT1），是一种在哺乳动物的多种功能中起作用的蛋白质，包括细胞衰老、应激抵抗和分化。SIRT1 也被证明与多种肿瘤有关。此外，最近已经批准了一些针对 SIRT1 的新的药物治疗方法。本研究的目的是使用免疫组织化学方法来描述人类软组织肿瘤中的 SIRT1 蛋白表达，希望找到新的诊断和治疗方法。在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/纤维组织细胞瘤、促结缔组织增生小圆细胞肿瘤、尤因肉瘤、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、孤立性纤维性肿瘤、滑膜肉瘤、未分化多形性肉瘤和肾母细胞瘤在内的 164 例软组织肿瘤中，对 SIRT1 免疫反应性进行了综述。此外，还测试了许多良性组织的 SIRT1 反应性。在非肿瘤组织中，所有前列腺基质、平滑肌和横纹肌中都观察到强烈的细胞质 SIRT1 反应性。在具有肌样分化的软组织肿瘤中观察到类似的细胞质 SIRT1 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。虽然 SIRT1 在肌样组织和沿这些线分化的肿瘤中的生理作用仍有待阐明，但这一观察结果表明该标志物在诊断免疫组织化学中可能具有潜在作用。此外，最近出现的能够选择性抑制 SIRT1 的药物有可能为靶向治疗提供潜在的应用。需要进一步的研究来进一步描述 SIRT1 在肌样组织和肿瘤中的作用。
