Pheochromocytomas are rare sympathoadrenal
tumors that are highly vascular. Their
malignancy is extremely difficult to estimate on the basis of histopathological features.
Vascular endothelial growth factor (
VEGF) is one of the most important angiogenic factors involved in both
tumor growth and
metastasis. In our search for new prognostic markers, we investigated the expression of
VEGF in normal adrenal gland, in 105 primary
pheochromocytomas, and in 6
metastases by using immunohistochemistry and Northern blot analysis. We also calculated the microvessel density of these
tumors by staining the endothelial cells with monoclonal CD34 antibody.
VEGF messenger
ribonucleic acid was found in all
pheochromocytomas studied. Immunohistochemically,
VEGF was not found in normal adrenal medullary cells. Interestingly, all malignant
pheochromocytomas (n=8), regardless of their primary location, had strong or moderate
VEGF immunoreactivity, while most benign adrenal
pheochromocytomas (26 of 37, 70.3%) were either negative or only weakly positive. The staining was heterogenous in extraadrenal
pheochromocytomas as well as in a group of
tumors that had histologically suspicious features but had not metastasized, here called borderline
tumors (n=29). The microvessel density varied greatly in all of the
tumor groups, and no statistical difference was found between these groups. Here we report moderate to strong
VEGF expression in malignant
pheochromocytomas, and negative or weak expression in benign adrenal
pheochromocytomas. Normal medullary cells are immunohistochemically negative. Thus, low
VEGF expression in
pheochromocytomas favors a benign diagnosis.