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The Correlation between EBP50 Expression Pattern and Metastatic Outcome of Renal Cell Carcinoma
renal cell carcinoma (RCC),Ezrin-radixin-moesin binding phosphoprotein 50 (EBP50 or NHERF1),metastasis,immunohistochemistry (IHC),
|Publication Year :||2008|
結果：在305個腎細胞癌患者的腫瘤組織中，有117個 (38.4%)細胞質呈現EBP50強陽性，這樣的患者較易發生癌症轉移 (p=0.03)；相反地，有65個 (21.3%)細胞核呈現EBP50強陽性的患者癌症轉移的風險較低 (p=0.043)。EBP50聚集在細胞質與腫瘤的細胞核分化分級有明顯的統計相關 (p=0.015)，類似的關係也可在細胞核呈EBP50陰性表現的腫瘤組織見到 (p=0.003)。以Kaplan-Meier方法得到的存活曲線發現只表現EBP50細胞質陽性顯然比只表現細胞核陽性的患者其無轉移存活期間明顯較短 (p=0.03)。EBP50的表現模式則與其他的危險因子，諸如性別、年齡、腫瘤大小、腫瘤分期與淋巴結轉移與否無關。
Renal cell carcinoma (RCC) accounts for 3% of adult malignancy and arises form renal tubular epithelium. The development of therapeutic modality against defined molecular target has been in a great demand since RCC patients with distant metastasis are notoriously resistant to chemotherapy and radiotherapy. Ezrin-radixin-moesin binding phosphoprotein 50 (EBP50) is initially identified from polarized epithelial cells as an adaptor protein linking integral membrane protein with cortical cytoskeleton. EBP50 also plays an important role in Wnt signaling pathway to promote cell proliferation. Recently, the expression patterns of EBP50 in human cancers have been addressed before, but functional characterization of EBP50 in RCC tumorigenesis is still controversial. To reveal its pathophysiological relevance, this study examined the expression pattern of EBP50 in a cohort of human renal cell carcinoma.
Methods: Three hundred and five RCC tissue specimens were examined by immunohistochemistry (IHC) and the subcellular expression pattern of EBP50 was correlated with standard clinicopathological parameters.
Results: Aberrant cytoplasmic expression of EBP50 was detected in 117 (38.4%) RCC patients who had significantly increased the latent metastasis potential (p=0.03). By contrast, 65 (21.3%) RCC patients, who displayed nuclear EBP50 immunoreactivity, exhibited lower metastasis potential (p=0.04). Cytoplasmic accumulation of EBP50 was found in RCC with higher nuclear grading (p=0.015), and the association is contrary to the nuclear localization of EBP50 (p=0.003) By Kaplan-Meier analysis, the metastasis-free survival of RCC patients with strong cytosolic EBP50 expression is significantly shorter than those with nuclear EBP50 immunoreactivity (p=0.03) . However, cellular expression pattern of EBP50 did not correlate with average age at time point of diagnosis, sex, tumor size, tumor staging and lymph node metastasis.
To reveal the molecular mechanism underlying the effect of EBP50 subcellular localization on cell migration and proliferating behaviors, Flag-EBP50_dEB, which expressed mainly in cytoplasm but not in nucleus, was stably expressed in human RCC cell line (CRL-1933). According to the results of wound healing, transwell, MTS assay and FACScan, the cytoplasmic accumulation of EBP50 increases migration ability and seems to have defective proliferation. This study provides observations implying that cytosolic expressed EBP50 promotes metastasis in RCC patients.
|Appears in Collections:||分子醫學研究所|
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