Endoglin (CD 105) as a potential prognostic factor in neuroblastoma.

BACKGROUND

Endoglin (CD105) is a cytokine that modulates angiogenesis by regulating different cellular functions, including endothelial proliferation, differentiation, migration and formation of microvessels. CD105 is expressed strongly in the tumor vasculature, and intratumoral microvessel density (IMVD), as determined by the use of antibodies to CD105, it has been found to be an important prognostic indicator for outcome in various malignances. This study aims to determine if the clinical outcome of children with neuroblastoma is correlated with IMVD, as determined by CD105 staining and other prognostic factors.

PROCEDURE

Tumor tissue specimens from 38 patients with peripheral neuroblastic tumors who underwent surgical resection or biopsy of their primary tumor without any preoperative therapy were retrospectively reviewed. IMVD was identified immunohistochemically using monoclonal antibodies against CD105. Prognostic factors, such as the MYCN oncogene, disease stage, histopathology and age, were correlated with outcome.

RESULTS

Among 38 examined specimens, the median IMVD value was 23.2 (15.1-28.4). The IMVD identified by CD105 was significantly higher in patients with unfavorable histology, metastatic disease, MYCN amplification and COG high risk group. ROC analysis was used to find significant IMVD level regarding EFS. The cut-off >18 was selected according to the greatest sensitivity (100%) and specificity (68.42%). The multivariate Cox proportional hazards analysis demonstrated that MYCN amplification and IMVD were significant prognostic factors in predicting EFS (hazard ratio for MYCN amplification: 3.61; 95% CI: 1.20-10.90; P = 0.023 and for IMVD: 1.05; 95% CI: 1.00-1.09; P = 0.037).

CONCLUSION

IMVD determined by CD105 appeared to be an independent prognostic factor for neuroblastoma.