[1709] Correlation between Vascular Endothelial Growth Factors Expression and Risk of Bone Marrow Metastasis in Children with Neuroblastoma.

Kari Hooper, Ali G Saad, Jailan M Osman. Arkansas Children's Hospital, Little Rock

Background: Neuroblastoma (NB) is a common pediatric neoplasm. Histopathological features remain a poor predictor of the risk of developing distant metastases, in particular bone marrow (BM) metastasis, in patients with NB. Despite significant advances in therapeutic protocols, the prognosis of children with NB remains largely poor. We conducted this study to investigate the correlation between the expression of various VEGFs in NB and the development of BM metastasis.
Design: Twelve patients (group 1) with NB and BM metastasis and 9 patients (group 2) with negative BM are included in this study. Slides from the primary tumor are immunostained with antibodies against VEGFR-1, VEGFR-2, VEGF-B, and VEGF-D. Each slide is scanned and the percentage of VEGF-positive blood vessels in the tumor is estimated using semi-quantitative method. The expression of each VEGF is correlated with the risk of developing BM metastasis.
Results: Group 1 (mean age 20.6 months; range 0.5-61 months) consisted of 7 males and 5 females. Group 2 (mean age 67.8 months; range 24-156 months) consisted of 3 males and 4 females. There was a statistical difference in the expression of VEGFR-1 and VEGF-B between both groups (P=0.02 and 3.04E-05, respectively). We observed no significant difference in the expression of VEGFR-2 between both groups (P=0.19). There was complete absence of expression of VEGF-D in both groups of patients. A significantly increased risk of BM metastasis was found in patients with high expression of VEGFR-1 and VEGF-B. It appears that VEGF-D plays no role in angiogenesis or tumor progression of NB. Details of the expression of various VEGF inlcuded in this study are summarized in table 1.

Table 1-VEGF expression in neuroblastoma

Neuroblastoma	VEGFR-1		VEGFR-2		VEGF-B
	Mean	Range	Mean	Range	Mean	Range
With BM metastasis	38.3	10-80	56	2-100	84	70-90
Without BM metastasis	12.5	0-50	68.9	50-100	36	10-60

Conclusions: Our study indicates that patients with neuroblastoma with high expression of VEGFR-1 and VEGF-B in their primary tumors have a greater risk of developing bone marrow metastasis. Our study suggests that patients with neuroblastoma and a specific biomarker expression may benefit from an individualized surveillance regimen and a preventive therapeutic intervention designed to prevent of delay the development of bone marrow metastasis. This preliminary study provides a promising tool that may help in the management of neuroblastoma patients in particular treatment with anti-VEGF targeted therapy.
Category: Pediatrics

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 222, Monday Morning