Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
Pathol Int. 2020 Jun;70(6):323-329. doi: 10.1111/pin.12913. Epub 2020 Feb 18.
The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry. We studied 18 patients of lymphatic anomalies, including lymphatic malformation (LM, n = 14), Kaposiform lymphangiomatosis (KLA, n = 2) and Kaposiform hemangioendothelioma (KHE, n = 2). Normal lymphatic vessels expressed 4EBP1, S6K1 and p-S6K1, but not p-4EBP1, mTOR or p-mTOR. The mTOR was detected in all lymphatic anomalies, whereas its activation form p-mTOR was detected in half cases of KLA and KHE but not in LM. All lymphatic anomalies expressed S6K1 and its activated form p-S6K1. The expression of 4EBP1 was also found in all lymphatic anomalies, but its activation was detected in approximately half of them. The activation of mTOR was seen in tumor (KLA and KHE) but not in malformation (LM), whereas the activation of S6K1 and 4EBP1 was seen in all and half of lymphatic anomalies, respectively.
哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂西罗莫司是治疗难治性淋巴异常的有效方法。然而，对于 mTOR 通路成分在淋巴异常中的表达知之甚少。在这里，我们通过免疫组织化学研究了 mTOR 通路成分及其磷酸化形式（mTOR、p-mTOR、4EBP1、p-4EBP1、S6K1 和 p-S6K1）在正常淋巴管和淋巴异常中的表达模式。我们研究了 18 例淋巴异常患者，包括淋巴管畸形（LM，n=14）、卡波西样淋巴管瘤病（KLA，n=2）和卡波西样血管内皮细胞瘤（KHE，n=2）。正常淋巴管表达 4EBP1、S6K1 和 p-S6K1，但不表达 p-4EBP1、mTOR 或 p-mTOR。所有的淋巴异常都检测到 mTOR，而其激活形式 p-mTOR 在一半的 KLA 和 KHE 病例中检测到，但在 LM 中未检测到。所有的淋巴异常都表达 S6K1 和其激活形式 p-S6K1。4EBP1 的表达也在所有的淋巴异常中被发现，但只有一半的病例检测到其激活。mTOR 的激活仅见于肿瘤（KLA 和 KHE），而不见于畸形（LM），而 S6K1 和 4EBP1 的激活分别见于所有和一半的淋巴异常。
