Identification of novel biomarkers in neuroblastoma associated with the risk for bone marrow metastasis: a pilot study

Neuroblastoma is a common pediatric neoplasm with variable histopathological features that carry an inherent risk of developing distant metastases, in particular bone marrow metastasis. Nestin, X-linked inhibitor of apoptosis (XIAP) and vascular growth factors (VEGF) are biomarkers that are implicated in the tumorigenesis of various cancers. We studied the expression of these biomarkers in neuroblastoma, in relation to bone marrow (BM) metastasis and other histologic parameters. Patients with neuroblastoma included seven with BM metastasis and 12 with non-metastatic tumors. Slides from the primary tumors were immunostained with antibodies against nestin, XIAP, VEGF-A, VEGF-B, VEGF-D, VEGF-R1, and VEGF-R2. Immunostaining results were evaluated by two pathologists, graded and statistically correlated with the risk of developing BM metastasis. Nestin was expressed in 16/19 cases with no significant difference between patients with BM metastasis and those without BM metastasis. XIAP was identified in 18/19 tumor cases; the staining density was significantly lower in patients with bone marrow metastasis and those with unfavorable histology. VEGF-R1, VEGF-R2, and VEGF-B were expressed while VEGF-A and VEGF-D were not. Significantly, higher expression of VEGF-B was noted in patients with BM metastasis. Expression of VEGF-B and XIAP in neuroblastoma may play a role in the development of bone marrow metastasis. Given the limited number of patients in this study, a larger cohort is needed to validate these findings.