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Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors
Author(s) -
Partanen Taina A.,
Alitalo Kari,
Miettinen Markku
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19991201)86:11<2406::aid-cncr31>3.0.co;2-e
Subject(s) - pathology , lymphangiogenesis , medicine , angiogenesis , lymphatic endothelium , lymphatic system , receptor tyrosine kinase , vascular endothelial growth factor , immunohistochemistry , neovascularization , cancer research , receptor , cancer , metastasis , vegf receptors
BACKGROUND Among the molecules important to angiogenesis and lymphangiogenesis is vascular endothelial growth factor receptor 3 (VEGFR‐3), a member of the receptor tyrosine kinases of endothelial cells. This receptor is expressed consistently in normal lymphatics, lymphangiomas, and in Kaposi sarcoma, but data regarding other vascular tumors are scant. METHODS In this study the authors immunohistochemically examined VEGFR‐3 expression in 82 benign, 31 borderline, and 72 malignant vascular tumors using a monoclonal antibody to VEGFR‐3, heat‐induced epitope retrieval, and an avidin‐biotin‐peroxidase detection system. RESULTS Although normal mesenchymal tissues showed VEGFR‐3 only in the lymphatics, benign and malignant vascular tumors and neovascularization of nonendothelial tumors showed widespread VEGFR‐3 distribution. All lymphangiomas and Kaposi sarcomas showed consistent VEGFR‐3 reactivity. Among the hemangiomas, spindle cell hemangiomas and 80% of capillary (including all lobular capillary hemangiomas) were positive whereas the endothelium of cavernous, venous, and epitheloid hemangiomas were positive in a minority of cases (20%, 27%, and 33%, respectively). Among the borderline lesions, Kaposiform hemangioendotheliomas were intensely positive whereas epithelioid hemangioendotheliomas were positive in 11 of 29 cases (38%). Angiosarcomas showed VEGRF‐3 reactivity in the majority of cases (48 of 60 cases; 80%). The nonepithelioid variants more often were positive (40 of 45 cases; 89%) than the epithelioid variants, of which 8 of 15 (53%) showed positive tumor cells. Nonvascular tumors (including perivascular tumors, other sarcomas, melanomas, carcinomas, and large cell lymphomas) consistently were negative whereas tumor neovascularization commonly was VEGFR‐3 positive. CONCLUSIONS The results of the current study show that although VEGFR‐3 shows specificity toward lymphatics in normal tissues, this receptor is distributed extensively in benign and malignant vascular tumors and therefore can be considered a novel marker in the assessment of endothelial cell differentiation of vascular neoplasms. Cancer 1999;86:2406–12. © 1999 American Cancer Society.