The Study Of Relationship Between Phosphorylation Of Fascin And Prognosis Of Patients With Esophageal Squamous Cell Carcinoma

Fascin, a structurally unique and evolutionarily actin cross-linking protein, could induce the membrane protrusions and increase cell motility of epithelial cells. Recent studies showed that Fascin is absent or very low expression in normal epithelium but upregulated in transformed cells and many kinds of human neoplasms, such as esophageal, gastric, colonic, pancreatic, lung, breast, ovarian, prostate and thyroid tumors, and high expression of Fascin is associated with poor survival of patients.Phosphorylation of Fascin at serine 39 (Phospho-S39-fascin) could inhibit its actin binding and bundling activities and decrease filopodia formation. However, the relationship between Phospho-S39-fascin expression and clinicopathological parameters in tumors is still unknown. Here western blot analysis and immunohistochemistry applied to tissue microarray technology were performed to examine the expression status of nonphosphsrylated Fascin (Fascin) and Phospho-S39-fascin and their impacts on the prognosis of patients with esophageal squamous cell carcinoma (ESCC).First, the expression of Fascin and Phospho-S39-fascin in 254 ESCC samples was tested by tissue microarray and immunohistochemistry method. Results showed that:In normal esophagus, Fascin was absent or only apparent in basal and lower spinous layer and Phospho-S39-fascin usually showed a little stronger immunoreactivity than Fascin; In ESCC tissues, Fascin and Phospho-S39-fascin expressions were tested by diffuse cytoplasmic staining, and stronger immunoreactivity was observed in infiltrative margins of cancer nests for Fascin, but not observed for Phospho-S39-fascin. Further Kaplan-Meier survival analysis revealed that high expression of Fascin was significantly associated with a poor prognosis of the ESCC patients (P=0.006). In contrast, high expression of Phospho-S39-fascin correlated significantly with an improved outcome of patients (P=0.016). Multivariate analysis showed that both Fascin and Phospho-S39-fascin were independent prognostic factors. In a combining analysis, the patients with high expression of Fascin and low expression of Phospho-S39-fascin tumors had a shorter overall survival than that with high expression of both Fascin and Phospho-S39-fascin rumors (5 year overall survival rate:28.7%vs.48.3%, P=0.068).Second, western blot analysis in 8 ESCC cell lines and 18 tissue specimens and paired adjacent normal epithelial tissues was performed to detect the expression of Fascin and Phospho-S39-fascin. And the results were in accordance with the immunohistochemistry.Our results suggest that high expression of Fascin correlates with poor prognosis and high expression of Phospho-S39-fascin correlates with improved prognosis in ESCC patients.