Microvessel density and VEGF/VEGF receptor status and their role in sarcomas of the pulmonary artery.
Neoangiogenesis, driven by a variety of angiogenic factors, plays an essential role during development and progression of malignant tumors. Vascular endothelial growth factor (VEGF) and its receptors have been designated a central part in the angiogenic process during malignancy. We studied the vascular parameters by means of morphology and morphometry in 7 sarcomas of the pulmonary artery (SPA) and 10 poorly differentiated leiomyosarcomas of soft tissue. Immunohistochemical analysis of VEGF and VEGFR was related to survival and prognosis. The microvessel density (MVD) and intervascular distances (IVD) differed significantly only at sites of necrosis compared to non-necrotic areas in SPA but not for soft tissue leiomyosarcomas. MVD, IVD and vascular surface area (VSA) revealed no difference between SPA and leiomyosarcomas of different origin. We found a more pronounced expression of VEGF in most tumors at sites of necrosis. The receptors were present in a subset of tumor vessels mostly at the tumor border. VEGFR-2 expression was also seen in a subset of tumor cells whereas VEGFR-1 showed only weak expression in some tumors. Local hypoxia seems to induce a higher MVD and a lower IVD at sites of necrosis compared to those areas without necrosis. The presence of necrosis in both sarcoma groups was correlated with the presence of VEGF due to local tumor hypoxia and subsequent up-regulation of VEGFR-2 and VEGFR-1 in tumor vessels as well as tumor cells. Overall and relapse-free survival showed no difference concerning all examined parameters. Thus, microvessel density does not seem to be a prognostic factor in SPA and other sarcomas.
Gaumann
Andreas K A
AK
Universitäts-klinikum Regensburg, Institut für Pathologie, Franz-Josef Strauss Allee 11, Regensburg, Germany. andreas.gaumann@klinik.uni-regensburg.de
Schermutzki
Gero
G
Mentzel
Thomas
T
Kirkpatrick
C James
CJ
Kriegsmann
Joerg B
JB
Konerding
Moritz A
MA
D000328:Adult; D000368:Aged; D002196:Capillaries / Q000473:pathology; D005169:Factor VIII / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011651:Pulmonary Artery; D012509:Sarcoma / Q000098:blood supply* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism*; D019043:Vascular Neoplasms / Q000098:blood supply* / Q000401:mortality* / Q000473:pathology
D042461:Vascular Endothelial Growth Factor A; D005169:Factor VIII; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2