Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures
Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures
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DOI：
10.1016/s0002-9440(10)63843-6
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发表时间：
2003-02-01
影响因子：
6
通讯作者：
Henske, EP
中科院分区：
文献类型：
--
作者：
Karbowniczek, M;Yu, J;Henske, EP
肾血管平滑肌脂肪瘤是一种偶发的高度血管性肿瘤，见于肺淋巴管肌瘤病（LAM）和结节性硬化症（TSC）。本研究的目的是确定血管平滑肌脂肪瘤的特殊血管是肿瘤性的还是反应性的。我们研究了LAM患者16p13染色体TSC2区域杂合性缺失（LOH）的血管平滑肌脂肪瘤。我们发现血管平滑肌脂肪瘤包含五种形态不同的血管类型：细胞型、胶原型、血管周细胞型、肾小球型和动脉瘤型。使用激光捕获显微解剖，我们确定四种血管类型有TSC2 LOH，因此是肿瘤。一种血管类型，胶原血管，没有LOH，可能是反应性的。最近，在缺乏TSC2表达的细胞中证实了S6激酶及其靶S6核糖体蛋白（S6）的活化。我们发现检测到LOH的血管平滑肌脂肪瘤血管类型对抗磷酸s6抗体有免疫反应。没有LOH的血管平滑肌脂肪瘤细胞，包括血管的内皮成分，没有免疫反应。据我们所知，血管平滑肌脂肪瘤是第一个以血管细胞而非基质细胞为肿瘤的良性血管肿瘤。血管平滑肌脂肪瘤似乎反映了新的血管机制，可能是激活涉及S6激酶的细胞通路的结果。
Renal angiomyolipomas are highly vascular tumors that occur sporadically, in women with pulmonary lymphangiomyomatosis (LAM), and in tuberous sclerosis complex (TSC). The goal of this study was to determine whether the distinctive vessels of angiomyolipomas are neoplastic or reactive. We studied angiomyolipomas with loss of heterozygosity (LOH) in the TSC2 region of chromosome 16p13 from patients with LAM. We found that angiomyolipomas contain five morphologically distinct vessel types: cellular, collagenous, hemangiopericytic, glomeruloid, and aneurysmatic. Using laser capture microdissection, we determined that four of the vessel types have TSC2 LOH and are therefore neoplastic. One vessel type, collagenous vessels, did not have LOH, and is presumably reactive. Recently, activation of S6 Kinase and its target S6 ribosomal protein (S6) was demonstrated in cells lacking TSC2 expression. We found that angiomyolipoma vessel types in which LOH were detected were immunoreactive with anti-phospho-S6 antibodies. Angiomyolipoma cells without LOH, including the endothelial component of the vessels, were not immunoreactive. To our knowledge, angiomyolipomas are the first benign vascular tumor in which the vascular cells, rather than the stromal cells, have been found to be neoplastic. Angiomyolipomas appear to reflect novel vascular mechanisms that may be the result of activation of cellular pathways involving S6 Kinase.