Expression and clinical significance of Wnt-1 and β-catenin in nasopharyngeal carcinoma

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Ai zheng = Aizheng = Chinese journal of cancer (Impact Factor: 2.16). 02/2009; 28(1):72-5.
Source: PubMed


As signaling molecule and key component of Wnt/beta-catenin signaling pathway respectively, Wnt-1 and beta-catenin are abnormally expressed in several malignancies and correlate with poor prognosis. This study was to investigate the expression and clinical significance of Wnt-1 and beta-catenin in nasopharyngeal carcinoma (NPC).
The expression of Wnt-1 and beta-catenin in 111 specimens of NPC was detected by SP immunohistochemistry. Their correlations to relapse-free survival (RFS), metastasis-free survival (MFS) and progression-free survival (PFS) were analyzed.
The high expression of beta-catenin was observed in 64 (57.7%) of the 111 cases. Its high expression rate was significantly higher in advanced NPC than in early stage NPC (63.1% vs. 40.7%, p = 0.041). The RFS, MFS and PFS were lower in high beta-catenin expression group than in low beta-catenin expression group (p < 0.05). Cox regression analysis demonstrated that beta-catenin was related to poor prognosis of NPC patients. The high expression of Wnt-1 was observed in 68 (61.3%) of the 111 cases, but its expression had no effect on RFS, MFS and PFS (p > 0.05).
Wnt/beta-catenin signaling pathway may be activated abnormally in some NPC patients. beta-catenin may be a prognostic factor of NPC.

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    • "Moreover, the levels of phosphorylated GSK-3β and intranuclear β-catenin have been shown to be higher in NPC cells after EBV infection [30]. The expression of β-catenin has been associated with advanced stages of NPC and inversely relates with the survival rate of patients [33]. It implies the important role of Wnt signaling pathway on the dysregulation of β-catenin in NPC. "
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is an uncommon cancer, which has a distinctive ethnic and geographic distribution. Etiology of NPC is considered to be related with a complex interaction of environmental and genetic factors as well as Epstein-Barr virus infection. Since NPC is located in the silent painless area, the disease is usually therefore diagnosed at the advanced stages; hence early detection of NPC is difficult. Furthermore, understanding in molecular pathogenesis is still lacking, pondering the identification of effective prognostic and diagnostic biomarkers. Dysregulation of signaling molecules in intracellular signal transduction, which regulate cell proliferation, apoptosis, and adhesion, underlines the basis of NPC pathogenesis. In this paper, the molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression. The important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
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    ABSTRACT: To investigate the role of β-catenin in pathogenesis of nasopharyngeal carcinoma (NPC). Cellular proliferation, apoptosis, matrix penetration assay, and western blotting were employed to determine cell biological changes in NPC cell lines transfected with β-catenin siRNA. Immunohistochemistry staining was used to detect β-catenin and Ki-67 expression in NPC tissue. β-Catenin was upregulated in NPC cell lines and tissues compared with chronic nasopharyngitis tissue. β-Catenin knockdown dramatically inhibited cellular growth, migration and invasion, but induced apoptosis of NPC cells. Further study showed that downstream genes of β-catenin signaling pathway including cyclin D1, c-Myc, MMP2 and MMP9 expression were suppressed in NPC cell lines transfected with β-catenin siRNA. Targeting β-catenin signaling pathway may be a noval strategy for NPC therapy.
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    ABSTRACT: Objective: To investigate the molecular mechanism of Wnt5a and Epstein-Barr virus latent membrane protein 1 (LMP1) aberrant expression in the nasopharyngeal carcinogenesis and to estimate if it can act as a molecular marker for nasopharyngeal cancer (NPC). Methods: Immunohistochemistry combined with previously made tissue microarrays were used to study the expression of Wnt5a and LMP1 in the nasopharyngeal carcinogenesis tissues. We investigated the role of over expression of Wnt5a and LMP1 in the development and progression of NPC and their relation with the clinicopathological features of NPC and whether they could act as molecular markers in benign and malignant NPC. Results: The positive percentage of Wnt5a and LMP1 protein expression in the NPC was significantly increased as compared with that in atypically hyperplastic nasopharyngeal epithelium, hyperplastic nasopharyngeal epithelium and histologically normal nasopharyngeal epithelium (P<0.05, P<0.01, and P<0.01). Wnt5a and LMP1 proteins were significantly higher in atypically hyperplastic nasopharyngeal epithelium than those in the hyperplastic nasopharyngeal epithelium and normal nasopharyngeal epithelium (P<0.05 and P<0.01). The positive expression of Wnt5a and LMP1 proteins in clinical T3 and T4 staged NPC was higher than that in clinical T1 and T2 staged NPC (P<0.01 and P<0.05). The positive expression of Wnt5a protein in the NPC with lymph node metastasis was higher than that in the NPC without lymph node metastasis (P<0.01). The positive percentage of LMP1 protein was significantly increased in non-keratinizing carcinoma compared with undifferentiated carcinoma and keratinizing carcinoma (P<0.05 and P<0.05). The expression of Wnt5a protein in the NPC had significant positive correlation with LMP1 (r=0.354, P<0.001). Combined molecular phenotype of both Wnt5a and LMP1 expression was a good marker to distinguish NPC from non-cancerous nasopharyngeal epithelium. Conclusion: The expression of Wnt5a and LMP1 protein in the NPC is positively correlated, and both wnt5a and LMP1 protein play important roles in the nasopharyngeal carcinogenesis either together or successively promoting the malignant transformation of nasopharyngeal epithelium and the development and progression of NPC. Both Wnt5a and LMP1 positive expression may act as good markers for NPC differential diagnosis.
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