title: The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues.
abstract: Detection of lymphatic endothelal cells (LECs) has been problematic because of the lack of specific markers. The homeobox transcription factor Prox1 is expressed in LECs of murine and avian embryos. We have studied expression of Prox1 in human tissues with immunofluorescence. In 19-wk-old human fetuses, Prox1 and vascular endothelial growth factor receptor-3 (VEGFR-3) are coexpressed in LECs of lymphatic trunks and lymphatic capillaries. Prox1 is located in the nucleus, and its expression is mutually exclusive with that of the blood vascular marker PAL-E. Prox1 is a constitutive marker of LECs and is found in tissues of healthy adults and lymphedema patients. Blood vascular endothelial cells (BECs) of hemangiomas express CD31 and CD34, but not Prox1. A subset of these cells is positive for VEGFR-3. Lymphatics in the periphery of hemangiomas express Prox1 and CD31, but not CD34. In lymphangiomas, LECs express Prox1, CD31, and VEGFR-3, but rarely CD34. In the stroma, spindle-shaped CD34-positive cells are present. We show that Prox1 is a reliable marker for LECs in normal and pathologic human tissues, coexpressed with VEGFR-3 and CD31. VEGFR-3 and CD34 are less reliable markers for LECs and BECs, respectively, because exceptions from their normal expression patterns are found in pathologic tissues.
authors.affiliation: Anatomisches Institut, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany. Joerg.Wilting@anat.uni-freiburg.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Wilting
authors.forename: Maria
authors.initials: M
authors.lastname: Papoutsi
authors.forename: Bodo
authors.initials: B
authors.lastname: Christ
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
authors.forename: Constantin S
authors.initials: CS
authors.lastname: von Kaisenberg
authors.forename: Jörg
authors.initials: J
authors.lastname: Borges
authors.forename: G Björn
authors.initials: GB
authors.lastname: Stark
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.forename: Jochen
authors.initials: J
authors.lastname: Rössler
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002675:Child, Preschool; D004729:Endothelium, Lymphatic / Q000737:chemistry* / Q000378:metabolism; D006391:Hemangioma / Q000737:chemistry; D018398:Homeodomain Proteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008202:Lymphangioma / Q000737:chemistry; D008206:Lymphatic Diseases / Q000378:metabolism*; D008209:Lymphedema / Q000378:metabolism; D009928:Organ Specificity; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis* / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3