Riedlinger Wolfram F J, Juraszek Amy L, Jenkins Kathy J, Nugent Alan W, Balasubramanian Sowmya, Calicchio Monica L, Kieran Mark W, Collins Tucker
Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Cardiovasc Pathol. 2006 Mar-Apr;15(2):91-9. doi: 10.1016/j.carpath.2005.11.006.
Primary pulmonary vein stenosis (PVS) is a progressive disorder of infants. Although catheter based intervention and chemotherapy are used to manage the disorder, the benefit of these approaches is reduced considerably by restenosis. The nature of the intimal cells causing the occlusive lesions in PVS is poorly understood.
Seven PVS cases were studied with antibodies for smooth muscle actin (SMA), muscle-specific actin (MSA), monoclonal desmin, S100 protein, CD31, CD34, CD45RO, CD68, CD99, Ki-67 (MIB-I), and with antibodies directed against several receptor tyrosine kinases (RTK), including platelet-derived growth factor alpha and beta receptor (PDGFR-alpha and -beta), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor 1 and 2 receptor (VEGFR), and stem cell factor receptor (c-kit).
Lesional cells stained strongly and diffusely with SMA and MSA, but not for macrophage, lymphocyte, endothelial markers, or for Ki-67. RTK expression was strong and diffuse for PDGFR-alpha and -beta, FGFR, and VEGFR-2. Lesional cells stained for VEGF and PDGF beta receptor was phosphorylated.
The histologic appearance, and the strong diffuse immunoreactivity for smooth muscle markers, indicates that the intimal lesional cells are myofibroblast-like. Expression of various receptor tyrosine kinases and some ligands suggests an autocrine or paracrine role of these proteins in the pathogenesis of the intimal occlusive lesion in PVS.
原发性肺静脉狭窄（PVS）是一种婴幼儿的进行性疾病。尽管基于导管的干预和化疗用于治疗该疾病，但这些方法的益处因再狭窄而大大降低。导致PVS闭塞性病变的内膜细胞的性质尚不清楚。
对7例PVS病例进行研究，使用针对平滑肌肌动蛋白（SMA）、肌肉特异性肌动蛋白（MSA）、单克隆结蛋白、S100蛋白、CD31、CD34、CD45RO、CD68、CD99、Ki-67（MIB-1）的抗体，以及针对几种受体酪氨酸激酶（RTK）的抗体，包括血小板衍生生长因子α和β受体（PDGFR-α和-β）、表皮生长因子受体（EGFR）、成纤维细胞生长因子受体（FGFR）、血管内皮生长因子1和2受体（VEGFR）以及干细胞因子受体（c-kit）。
病变细胞对SMA和MSA呈强烈弥漫性染色，但对巨噬细胞、淋巴细胞、内皮标志物或Ki-67无染色。PDGFR-α和-β、FGFR以及VEGFR-2的RTK表达强烈且弥漫。病变细胞对VEGF染色，且PDGFβ受体磷酸化。
组织学表现以及对平滑肌标志物的强烈弥漫性免疫反应表明，内膜病变细胞呈肌成纤维细胞样。各种受体酪氨酸激酶和一些配体的表达表明这些蛋白在PVS内膜闭塞性病变的发病机制中起自分泌或旁分泌作用。
