Vascular Endothelial Growth Factor Receptor-2 and Vascular Endothelial Growth Factor-A Are Localized Primarily to the Vasculature in Pilomyxoid Astrocytoma: A Comparative Study with Juvenile Pilocytic Astrocytoma.
Shree G Sharma, Ali G Saad. Arkansas Children's Hospital, Little Rock
Background: In recent WHO classification, pilomyxoid astrocytoma (PMA) has been added into the category of histological variants of pilocytic astrocytoma (PA). While PMA often show focal features of PA, it has a more aggressive clinical course. Vascular endothelial growth factor (VEGF) signaling is key to physiologic and pathologic angiogenesis and lymphangiogenesis, and is an established target in the development of anticancer therapeutics. VEGF-A is an important driver of the neovascular growth required to support solid tumor progression. The primary signaling receptor for VEGF-A is VEGFR-2, and activation of VEGFR-2 by VEGF-A directs the migration and extension of sprouting vessels.
Design: Six PMAs and 15 PAs are included in this study. Five cases of PMAs were identified by reviewing all cases of PAs on files in the Department of Pathology at Arkansas Children's Hospital since 1970. PAs cases consisted of the last 15 cases accessed in our files. In each case, three 4-µm-thick sections were performed and immunostained with antibody against VEGFR-2, and VEGF-A. The results are correlated with clinical prognosis.
Results: PMAs cases consisted of 4 males and 2 females (median age 3.5 years). PAs cases consisted of 9 males and 7 females (median age 7.9 years). Patients were followed up for a median time of 5.75 years (range 1.15-16.56 years) after the first diagnosis. Median disease-free interval was 2.3 years in patients with PMAs and 7.7 years in PA. Recurrence occured in 4 patients with PMAs and in 2 patients with PA. VEGFR-2 were expressed on vascular endothelium but not on malignant cells in six PMAs and focally on endothelial cells and malignant cells in two PMAs. There was a strong correlation between the expression of VEGFR-2 (P=0.009) and VEGF-A (P=0.01) on vascular endothelium and shorter disease-free survival rate. When VEGFR-2 and VEGF-A were expressed on endothelial and tumor cells, the disease-free survival rate decreased significantly (P=0.0008). No expression of VEGFR-2 or VEGF-A was observed in patients with PA including the case with recurrence. months after surgery. No statistical correlation was attempted (only one case).
Conclusions: We demonstrate for the first time the preferential expression of VEGFR-2, and VEGF-A in intratumoral vasculature and focally on tumor cells in patients with PMAs. The expression of VEGF may account for the high rate of recurrence in patients with PMAs. Furthermore, patients with PMAs may benefit from anti-VEGF targeted therapy.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 210, Monday Morning