| Background and ObjectiveEsophageal cancer is one of the most common malignant tumors, especially in some areas of China. The morbidity and mortality of esophageal cancer is the highest in local malignant tumor in some areas, this seriously affect the health of people. Infiltration and aversion are two tough problems in clinic therapy. They are also lethal factors for most patients. Therefore, there are more and more studies foucus on how to elevate early stage and monitor its aversion. HMGB1 is a non-histone, nuclear DNA-binding protein. HMGB1 is a versatile protein with intranuclear and extracellular functions,such as transcription, DNA repair, and response to infection and inflammation. HMGB1 has been recently demonstrated to paly an important role in many types of cancers. The role of HMGB1 and RAGE in esophagus carcinoma is unknown. To investigate the expression of HMGB1, RAGE and VEGF in esophagus squamous cell carcinoma. The immunohistochemical S-P method was used to detect expression of HMGB1, RAGE and VEGF in 51 esophagus squamous cell carcinoma tissues and 12 normal tissues, and to study the significance of expression of HMGB1, RAGE and VEGF protein. Explore esophageal lymph node metastases, molecular mechanism of comprehensive treatment for esophageal provides new ideas. This study is to explore the mechanism and interrelation of them in the incidence, infiltrating and metastasis. It provids a new rationale to therapy and judgement of prognosis of esophageal carcinoma.Materials and methodsS-P Immunohistochemical studies were performed in all 51 cases with esophageal squamous cell carcinoma, the expression of HMGB1,RAGE and VEGF was detected in Esophageal carcinoma and normal esophageal tissues. The results were analyzed with the clinical parameters. Statistical SPSS software 13.0 was used in the study.χ2 test, Fisher test and spearman rank correlation were used to analyze the difference of the results, the P value less than 0.05 was considered as significant.Results1. The expression of HMGB1 in esophageal squamous cell carcinomaImmunohistochemical studies were performed in all 51 cases with esophageal squamous cell carcinoma. Immunostaining for HMGB1 in tumor cells were observed in nuclei and cytoplasm, the positive rate of HMGB1 was 68.6% in esophageal cancer,16.7% in normal tissues. There was a significant difference between two groups (P<0.01).the association between HMGB1 expression and clinicopathological characteristics of tumors was examined. There was no significant correlation between HMGB1 expression and gender, age, differentiation degree or T classification (p>0.05). However, HMGB1 expression was positively correlated with N classification (P<0.05). A trend that patients with high HMGB1 expression had a partial response to tumor size and T classification in the entire cohort was found, but there was no correlation between HMGB1 expression and tumor size and T classification.2. RAGE in esophageal squamous cell carcinomaRAGE protein was detected in 26 cases. The positive rate is 51%.RAGE staining was mostly observed in the cytoplasm and membran of carcinoma cells. RAGE staining was weaker in normal tissues than in NPC tissues. There was significantly different between groups with high and low expression of RAGE.According to results, there was was no significant correlation between RAGE expression and gender, age, differentiation degree or T classification (p>0.05). However, RAGE expression was positively correlated with N classification (P<0.05). There is a similar with the exprssion of HMGB1 in tumor size and T classification, a trend that patients with high HMGB1 expression had a partial response to tumor size and T classification in the entire cohort was found.3. VEGF in esophageal squamous cell carcinomaThe positive rate of VEGF is higher than in normal control group (56.9% vs 8.3%, P<0.01). There is a significantly different between esophageal carcinoma group and normal control group. Over expression of VEGF was significantly correlated with N classification (P<0.05). No significant correlation was found between RAGE expression and gender, age, differentiation degree or T classification (p>0.05).4. The correlation of expression among HMGB1, RAGE and VEGF in esophageal squamous cell carcinomaThere was a positive correlation of the positive expression between HMGB1 and RAGE (r=0.520, P<0.01). The expression of HMGB1 is correlation with the VEGF (r=0.350, P<0.05). There was a positive correlation of the positive expression between VEGF and RAGE (r=0.413, P<0.01)Conclusions1 The expression of HMGBl, RAGE and VEGF is increased in esophageal carcinoma. It suggests that HMGB1, RAGE and VEGF overexpression has a role in the incident of esophageal carcinoma. Inflammation is associated with tumor.2 Overexpression of HMGB1, RAGE and VEGF is a associated with lymphatic metastasis in human esophageal squamous cell carcinoma. It support that overexpression of HMGB1, RAGE and VEGF has a role in the lymphatic metastasis.3 In human esophageal squamous cell carcinoma, there is correlation in HMGB1, RAGE and VEGF. HMGB1, RAGE and VEGF interact with each other play an important role in incident of esophageal carcinoma and lymphatic metastasis. 4 HMGB1, RAGE and VEGF may play a synergistic action in oncogenesis and lymphatic metastasis of esophageal carcinoma. The expression of HMGB1, RAGE and VEGF is detected may contribute to evaluate the statue of lymphatic metastasis and study the mechanism of lymphatic metastasis. Our study may provide a new target for gene therapy of esophageal carcinoma.
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