Expression Of Hedgehog Pathway Components Is Associated With Nasopharyngeal Carcinoma Lymph Node Metastasis And Lymphangiogenesis

Objective: To investigate the Shh, Ptch1, Smo and Gli-1 protein expression in nasopharyngeal carcinoma and correlate with lymph node metastasis and lymphangiogenesis. Method: Applying Shh,Gli-1 rabbit monoclonal antibody and Ptch1, Smo polyclonal rabbit antibody and D2-40 monoclonal antibody with immunohistochemistry(IHC) detect Shh, Ptch1, Gli-1 and Smo protein expression and lymphatic vessel density(LVD) in nasopharyngeal carcinomas(n = 69) in comparison to human normal nasopharyngeal epithelial tissues(n = 15). Using SPSS18.0 Analysis Software, immune reaction each score(expression level) between each group compared with application t test; Difference(positive or negative rate)between each group compared with χ2 test or Fisher,s Exact test. The correlation between protein expression of components by the Spearman rank correlation ananlysis.And, with P<0.05 judegement for the difference is statistically significant. The relationship between protein expression and the clinicopathological characteristics and lymphatic vessel density(LVD) in nasopharyngeal carcinoma were analysed. Result: The comprehensive scores(IRS) of Shh, Ptch1, Smo or Gli-1 protein expression in nasopharyngeal carcinomas were higher than human normal nasopharyngeal epithelial tissues(6.59±3.66 V,s 3.20±1.82,4.77±3.52 V.s 2.53±2.00,6.39±3.55 V,s 3.00±1.65、6.26±3.91 V.s 2.73±2.02,P<0.05,respectively). Over expression of Shh protein in nasopharyngeal carcinomas significantly correlated with clinical stages and lymph node metastasis(P<0.05). Over expression of Gli-1 protein in nasopharyngeal carcinomas significantly correlated with lymph node metastasis(P<0.05). Moreover, Shh and Gli-1 expression were positively correlated with high lymphatic vessel density(r=0.382, r=0.464, P=0.001, P<0.01). Ptch1 protein and Smo protein have no relation with LVD(r=0.088, 0.124; P=0.472, 0.311, respectively). Shh expression were correlated with Ptch1 expression and Gli-1 expression(r=0.456, 0.452; P<0.001, respectively);Ptch1 expression were correlated with Gli-1 expression(r=0.409, P<0.001);Smo expression were correlated with Gli-1 expression(r=0.383, P<0.001);Smo expression were no correlated with Shh expression and Gli-1 expression(r=0.179 and r=0.089, P=0.141 and P=0.182,respectively). Conclusion: It is demonstrated that Hh signaling pathway is abnormal activated in nasopharyngeal carcinoma. And the over expression of of Hh pathway components plays a crucial role during lymph angiogenesis and lymph node metastasis in nasopharyngeal carcinoma. Blocking Hh signaling pathways as targets for cancer treatment will become the new direction.