| Background and purpose Epithelial-mesenchymal transition (EMT) is an important mechanism of cancer invasion and metastasis. Novel blood and lymphatic vessel formations are related with tumor invasion and metastasis. Studies demonstrated that tumors got invasion and metastasis by EMT, neoangiogenesis and lymphogenesis. This study explored the expression of EMT-related markers E-cadherin, N-cadherin, angiogenesis marker CD34and lymphogenesis marker D2-40in nasopharyngeal carcinoma (NPC) and their relationship. In addition, we analyzed the relationship between these markers and clinicopathological features and prognosis of pharyngeal carcinoma. Further studies about the relationship between these markers and radiotherapy’s local control rate, and intensity-modulated radiotherapy’s reverse expression of these markers were also done to preliminary discuss their roles and clinical applications in this disease.Methods The expressions of E-cadherin, N-cadherin, CD34and D2-40were detected using immunohistochemistry in160cases of NPC tissue samples, and analyzed quantitatively by computer-aided image analysis system. The relationships between these markers and clinicopathological features of NPC investigated through Spearman rank correlation analysis. Risk factors of recurrence and metastasis of NPC were studied by univariate and Logistic multivariate regression analysis. The relationships between these markers and prognosis were explored using Kaplan-Meier method and Log-rank test. The relationships between these markers and shrinkage of tumor volume were studied in83patients received Intensity Modulated Radiation Therapy (IMRT) using Fisher’s exact test.Results E-cadherin expressed mainly in cell membrane and cytoplasm, pale-brown or brown, diffuse or focal distribution, with immunohistochemical positive index (IHCPI)1.250±0.454(95%CI1.182～1.315) in NPC; N-cadherin mai nly in cell membrane and cytoplasm, brownish yellow or dark brown, diffuse distribution, with IHCPI0.735±0.338(95%CI0.684～0.785). Lymphatic vessels markered by D2-40had consistent lumen structure, brownish-yellow, showing a layer of thin-walled, few lymphocytes within the lumen, no red blood cells, with IHCPI0.122±0.127 (95%CI0.102～0.141). Microvascular vessels markered by CD34show staining of vascular endothelial cells, brownish yellow or dark brown, diffuse distribution, with IHCPI0.116±0.061(95%CI0.106～0.125). E-cadherin downregulation and N-cadherin upregulation were correlated with lymph node metastasis, tumor stage, and recurrence and metastasis in NPC. CD34correlated with tumor stage, while D2-40correlated with lymphatic metastasis. The relationships between these markers and patient’s age and gender were not significant (P>0.05). Spearman rank correlation test showed that relationships between E-cadherin and N-cadherin, E-cadherin and D2-40were negative, while that between CD34and D2-40was positive.Univariate analysis showed that E-cadherin, N-cadherin, CD34and D2-40expression correlated significantly with recurrent and metastasis of NPC (P<0.05). Multivariate analysis showed that E-cadherin and CD34were independent risk factors of recurrence and metastasis of NPC. NPC patients with down-regulation of E-cadherin, and up-regulation of N-cadherin, CD34and D2-40had poor prognosis, and vice versa.Fisher’s exact test showed that70Gy was better than50Gy for primary tumor and cervical lymph node metastasis regression in NPC patients. IMRT group was superior to conventional radiotherapy group, with the difference statistically significant (P<0.05). Tumors with high expression of E-cadherin had more regression than those with low expression. However, tumors with low expression of N-cadherin had more regression than those with high expression. The differences between these groups had statistically significances (P<0.05). There was no difference between IMRT group and conventional radiotherapy group for primary tumor regression rate in NPC patients with high expression of CD34. But there was significant difference between these two groups with low expression of CD34, IMRT group was superior to conventional radiotherapy group (P<0.05). There was no difference between IMRT group and conventional radiotherapy group for primary tumor regression rate in NPC patients with high expression of D2-40. But there was significant difference between these two groups with low expression of D2-40, IMRT group was superior to conventional radiotherapy group (P<0.05).Conclusions EMT exists in NPC. E-cadherin had low expression, while N-cadherin had high expression in NPC. There may be E-cadherin conversion to N-cadherin. There were also lymphangiogenesis and neoangiogenesis in NPC, with correlations between them. Lymphangiogenesis correlateed with metastasis of lymph node, while Neoangiogenesis correlateed with tumor T and clinical stages. Combined detection of E-Cad, N-Cad, CD34and D2-40had predictive value for evaluation of invasion, metastasis and prognosis of nasopharyngeal carcinoma. IMRT was similar to conventional radiotherapy for NPC tumor regression rate in early stage. It suggested that the fractionated dose for every time could be decreased, which is beneficial to protect the normal tissue surrounded the tumor. However, IMRT was superior to conventional radiotherapy for tumor regression rates in advanced stage. In patients with low expression of CD34and low expression of D2-40, IMRT was superior to conventional radiotherapy for tumor regression rates. It was considered to be the reason that IMRT increased the efficiency by increasing the fractionated dose. Different expressions of invasive markers in NPC patients correlated to primary tumor regression rate. IMRT was superior to conventional radiotherapy for tumor regression rates. Thus, we speculate that IMRT may reverse the invasive process of NPC. |
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