Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells.
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.
Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Wolfram F J
WF
Riedlinger
Amy L
AL
Juraszek
Kathy J
KJ
Jenkins
Alan W
AW
Nugent
Sowmya
S
Balasubramanian
Monica L
ML
Calicchio
Mark W
MW
Kieran
Tucker
T
Collins
D000818:Animals; D003251:Constriction, Pathologic / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011667:Pulmonary Veins / Q000473:pathology*; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017539:Tunica Intima / Q000473:pathology; D014652:Vascular Diseases / Q000201:enzymology / Q000473:pathology
D020794:Receptor Protein-Tyrosine Kinases