COX-2 and Survivin Expression in Neuroblastomas Associated with Tumor Growth and Behavior

Angiogenesis and apoptosis are essential in the tumorigenesis and progression of various tumors. Cyclooxygenase-2 (COX-2) and survivin are important factors in these events; however, their roles in neuroblastomas are yet to be delineated. The aim of this study was to evaluate the expression of both COX-2 and survivin in neuroblastomas along with their relationships with tumor angiogenesis, apoptosis, and classical prognostic factors. hirty-nine various-stage neuroblastomas were evaluated for COX-2 expression, microvessel density (MVD), and survivin expression by immunohistochemical methods. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). Thirty-seven cases (94.9%) showed specific expression of COX-2 in the cytoplasm of the tumor cells. COX-2 expression correlated with International Neuroblastoma Staining System (INSS) stage (p=0.004), Shimada histology (p=0.006), and International Neuroblastoma Risk Group (INRG) risk factors (p=0.003). COX-2 expression was positively correlated with MVD (p=0.029), but not with apoptotic index (AI). Thirty-six cases (92.3%) showed positive survivin immunoreactivity, which was observed in the nucleus, cytoplasm, or both of tumor cells. Survivin expression correlated with patient age (p=0.019), INSS stage (p=0.001), and INRG risk factor (p <0.001). There was a significant difference in AI between the survivin-positive and the survivin-negative groups (p=0.018), and the AI was inversely correlated with survivin. The expression of COX-2 was closely correlated with the expression of survivin. COX-2 and survivin are overexpressed in neuroblastomas, which may play an important role by stimulating tumor angiogenesis and anti-apoptosis in neuroblastomas.