Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma.
Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n=18), TA (n=13), infantile hemangioma (n=13), pyogenic granuloma (n=18), and granulation tissue (n=13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1, podoplanin, LYVE-1, CD31, and CD34, whereas endothelial cells within glomeruloid foci were Prox1, podoplanin, LYVE-1, CD31, and CD34. The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Aude Rimella
AR
Le Huu
Chris H
CH
Jokinen
Brian P
BP
Rubin
Brian P
BP
Ruben
Martin C
MC
Mihm
Sharon W
SW
Weiss
Paula E
PE
North
Soheil S
SS
Dadras
D000293:Adolescent; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000737:chemistry; D003937:Diagnosis, Differential; D017789:Granuloma, Pyogenic / Q000378:metabolism; D006390:Hemangioendothelioma / Q000737:chemistry* / Q000145:classification / Q000175:diagnosis; D006391:Hemangioma / Q000737:chemistry* / Q000145:classification / Q000175:diagnosis; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007223:Infant; D008562:Membrane Glycoproteins / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011237:Predictive Value of Tests; D012878:Skin Neoplasms / Q000737:chemistry* / Q000145:classification / Q000175:diagnosis; D012983:Soft Tissue Neoplasms / Q000737:chemistry* / Q000145:classification / Q000175:diagnosis; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D033921:Vesicular Transport Proteins / Q000032:analysis; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin