Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies

Vascular endothelial growth factors ( VEGF)- A, - C and - D are
members of the proangiogenic VEGF family of glycoproteins. VEGF-A
is known to be the most important angiogenic factor under
physiological and pathological conditions, while VEGF-C and VEGF-D
are implicated in the development and sprouting of lymphatic
vessels, so called lymphangiogenesis. Local tumor progression,
lymph node metastases and hematogenous tumor spread are important
prognostic factors for esophageal carcinoma ( EC), one of the most
lethal malignancies throughout the world. We found solid evidence
in the literature that VEGF expression contributes to tumor
angiogenesis, tumor progression and lymph node metastasis in
esophageal squamous cell carcinoma ( SCC), and many authors could
show a prognostic value for VEGF-assessment. In adenocarcinoma (AC)
of the esophagus angiogenic properties are acquired in early
stages, particularly in precancerous lesions like Barrett's
dysplasia. However, VEGF expression fails to give prognostic
information in AC of the esophagus. VEGF-C and VEGF-D were detected
in SCC and dysplastic lesions, but not in normal mucosa of the
esophagus. VEGF-C expression might be associated with lymphatic
tumor invasion, lymph node metastases and advanced disease in
esophageal SCC and AC. Therapeutic interference with VEGF signaling
may prove to be a promising way of anti-angiogenic co-treatment in
esophageal carcinoma. However, concrete clinical data are still
pending.