Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas

Abstract

Background Angiosarcomas are malignant mesenchymal neoplasms, including sarcomas of presumptive vascular endothelial origin and sarcomas of probable lymphatic origin. It is, however, often difficult to determine whether they are from blood vascular or lymphatic endothelium. The majority of angiosarcomas are thought to originate from vascular endothelia and spread via bloodstream to lung, but lymphatic metastases can occur. Methods We investigated immunohistochemical expression of vascular endothelial growth factors (VEGF‐A, VEGF‐C) and their receptors (VEGFR‐1, VEGFR‐2, VEGFR‐3) in a series of 34 angiosarcomas. Results VEGF‐A was expressed by 32/34 (94%), VEGF‐C by 4/34 (12%), VEGFR‐1 by 32/34 (94%), VEGFR‐2 by 22/34 (65%), and VEGFR‐3 by 27/34 (79%). Patients who expressed low or no VEGFR‐2 showed a significantly unfavorable prognosis by log‐rank test (P = 0.010) and multivariate analysis (hazard ratio, 5.16; 95% CI, 1.40–19.04; P = 0.014). VEGFR‐1 and VEGFR‐3 were not significantly associated with patients' prognosis. Conclusions VEGF‐A and VEGFR‐1 were detected in diverse subtypes of angiosarcomas. In cooperation, VEGF‐A and VEGF‐C are likely to be involved in the development of angiosarcoma associated with lymphedema. VEGF‐C expression may cause susceptibility to lymphatic metastasis through tumor lymphangiogenesis. Angiosarcoma of the scalp, which is traditionally considered as a true hemangiosarcoma, may include some cases of lymphatic origin. J. Surg. Oncol. 2008;97:74–81. © 2007 Wiley‐Liss, Inc.

Akt1 and Akt3 Exert Opposing Roles in the Regulation of Vascular Tumor Growth

“…In infantile hemangioma, hemangioma-derived endothelial cells (hemeEC) have constitutively active VEGF receptor-2 signaling with high phosphorylation levels of ERK1/2 and Akt (3). Human angiosarcoma expresses VEGF-A and the VEGF receptors (4). We have shown increased phosphorylation of Akt and 4E-BP1 in angiosarcoma (5).…”

Thalidomide Combined with Neoadjuvant Chemotherapy in Angiosarcoma of the Breast with Complete Pathologic Response: Case Report and Review of Literature

“…Immunohistochemical data from Itakura et al [16] demonstrated positive VEGFR-3 expression in 27 of 34 (79%) angiosarcomas; however none of these had breast origin. Gennaro et al [12], searching for VEGF re-expression, determined its expression levels in 20 breast specimens and found a significant association with low- and intermediate-grade tumors, suggesting the role of VEGF in the early carcinogenesis of angiosarcoma.…”

Novel Therapeutic Targets in Soft Tissue Sarcomas

“…[108][109][110] Various reports have demonstrated overexpression of VEGFR-2 and VEGFR-3 and their corresponding ligands, VEGF-A, VEGF-C, in pulmonary and cutaneous angiosarcomas, denoting the paracrine and/or autocrine role in their development and proliferation. 90,124,125 Alveolar soft part sarcoma (ASPS) is known to be chemotherapy resistant and therefore development of novel agents is essential. Stacchioti et al 126 reported a series of 10 patients.…”