Shen Jia, Shrestha Swati, Rao P Nagesh, Asatrian Greg, Scott Michelle A, Nguyen Vi, Giacomelli Paulina, Soo Chia, Ting Kang, Eilber Fritz C, Peault Bruno, Dry Sarah M, James Aaron W
School of Dentistry, University of California, Los Angeles, CA 90095.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Hum Pathol. 2016 Aug;54:92-9. doi: 10.1016/j.humpath.2016.03.008. Epub 2016 Apr 8.
Pericytes are modified smooth muscle cells that closely enwrap small blood vessels, regulating and supporting the microvasculature through direct endothelial contact. Pericytes demonstrate a distinct immunohistochemical profile, including expression of smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Previously, pericyte-related antigens have been observed to be present among a group of soft tissue tumors with a perivascular growth pattern, including glomus tumor, myopericytoma, and angioleiomyoma. Similarly, malignant tumor cells have been shown to have a pericyte-like immunoprofile when present in a perivascular location, seen in malignant melanoma, glioblastoma, and adenocarcinoma. Here, we examine well-differentiated liposarcoma specimens, which showed some element of perivascular areas with the appearance of smooth muscle (n = 7 tumors). Immunohistochemical staining was performed for pericyte antigens, including smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Results showed consistent pericytic marker expression among liposarcoma tumor cells within a perivascular distribution. MDM2 immunohistochemistry and fluorescence in situ hybridization for MDM2 revealed that these perivascular cells were of tumor origin (7/7 tumors), whereas double immunohistochemical detection for CD31/CD146 ruled out an endothelial cell contribution. These findings further support the concept of pericytic mimicry, already established in diverse malignancies, and its presence in well-differentiated liposarcoma. The extent to which pericytic mimicry has prognostic significance in liposarcoma is as yet unknown.
周细胞是一种经过修饰的平滑肌细胞,紧密包裹小血管,通过与内皮细胞直接接触来调节和支持微血管系统。周细胞具有独特的免疫组织化学特征,包括平滑肌肌动蛋白、CD146、血小板衍生生长因子受体β和G蛋白信号调节因子5的表达。此前,已观察到周细胞相关抗原存在于一组具有血管周围生长模式的软组织肿瘤中,包括血管球瘤、肌周细胞瘤和血管平滑肌瘤。同样,恶性肿瘤细胞在血管周围位置时也表现出类似周细胞的免疫特征,如恶性黑色素瘤、胶质母细胞瘤和腺癌。在此,我们检查了高分化脂肪肉瘤标本(n = 7个肿瘤),这些标本显示出一些血管周围区域有平滑肌样外观。对周细胞抗原进行了免疫组织化学染色,包括平滑肌肌动蛋白、CD146、血小板衍生生长因子受体β和G蛋白信号调节因子5。结果显示,脂肪肉瘤肿瘤细胞在血管周围分布中一致表达周细胞标志物。MDM2免疫组织化学和MDM2荧光原位杂交显示,这些血管周围细胞起源于肿瘤(7/7个肿瘤),而CD31/CD146双重免疫组织化学检测排除了内皮细胞的作用。这些发现进一步支持了在多种恶性肿瘤中已确立的周细胞模拟概念及其在高分化脂肪肉瘤中的存在。周细胞模拟在脂肪肉瘤中具有预后意义的程度尚不清楚。