Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells

Wolfram F. J. Riedlinger, Amy L. Juraszek, Kathy J. Jenkins, Alan W. Nugent, Sowmya Balasubramanian, Monica L. Calicchio, Mark W. Kieran, Tucker Collins

Children’s Hospital Boston and Harvard Medical School.
United States

Cardiovascular Pathology
Cardiovasc Pathol 2006; 15: 91-99
DOI: 10.1016/j.carpath.2005.11.006

Abstract
Background: 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.
Methods: 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).
Results: 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.
Conclusions: 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.

Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Pulmonary Venous Pathology

Year of Publication: 2006

Age Focus: Pediatric

Article Type: Case Reports or Retrospective Observations in Small Groups of Patients (≤10 patients). Studies of Vascular Biology and Mechanism of Disease.

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