Chonnam Med J.  2009 Apr;45(1):9-18. 10.4068/cmj.2009.45.1.9.

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

• Park AR
• Kim HS
• Park CS

• KMID: 2172278
• DOI: http://doi.org/10.4068/cmj.2009.45.1.9

Abstract

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.

Keyword

Neuroblastoma; COX-2; Survivin; Angiogenesis; Apoptosis

MeSH Terms

Apoptosis
Cell Transformation, Neoplastic
Cyclooxygenase 2
Cytoplasm
DNA Nucleotidylexotransferase
Humans
Microvessels
Neuroblastoma
Risk Factors
Cyclooxygenase 2
DNA Nucleotidylexotransferase

Figure

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  Fig. 1 MVD count was performed on the captured image by touch count (original maginification, ×200).

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  Fig. 2 Immunohistochemiscal staining of COX-2. Specific COX-2 expression in the cytoplasm of tumor cells in neuroblastoma, Schwannian stroma-poor (A), differentiating neuroblasts with nuclear and cytoplasmic differentiation (B), tumor-derived differentiated ganglion in ganglioneuroma (C), and adrenal cortex in non-malignant adrenal tissue (D) were noted (COX-2 immunostaining, original maginification, ×200).

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  Fig. 3 Immunohistochemical staining of Survivin in neuroblastoma. Different distributions of survivin expression were noted in nucleus of Schwannian stroma-poor, undifferentiated subtype (A), cytoplasm in neuroblasts with cytoplasmic differentiation of Schwannian stroma-poor, differentiating subtype (B), and both areas in neuroblasts of Schwannian stroma-poor, poorly differentiated subtype (C). In the Schwannian stroma-poor, poorly differentiated subtype case, low survivin expression in nucleus are also noted (D) (Survivin Immunohistochemistry, ×200).

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  Fig. 4 Apoptotic cells (arrows) are shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique (TUNEL assay, original maginification, ×200).

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