Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas.
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.
Itakura
Eijun
E
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
Hidetaka
H
Oda
Yoshinao
Y
Tsuneyoshi
Masazumi
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006394:Hemangiosarcoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor