Alternations Of Survivin, VEGF And E-cadherin And Esophageal Cancer Prognosis On The Patients From The High-incidence Area For Esophageal Cancer In Linzhou, Henan

Esophageal carcinoma (EC) is one of the six most common malignant diseases inthe world. Linzhou city (formerly Linxian) and nearby counties in Henan province, has been well recongnized as the highest incidence and mortality areas for EC in the world. The five-year survival rate for early esophageal cancer patients is more than 90%, however, patients at late or advanced stage are very poor, with a five-year survivial rate of less than 10%. The invasion and metastasis of cancer cell lacking of sensitive and specific therapy reagent are the key ponit leading to the recurrence of EC and death of patients. But the mechanism of invasion and metastasis of EC is largely unknown, so be the significance of the marker evaluating patients'prognosis.So far, traditional prognostic markers, such as cancer stage based on clinical stage and pathological grade is still used to evaluate the prognosis of EC patients. However, it has been well recognized that there is discordance between the traditional prognosis biomarkers and the actual prognosis, for example, the patients with well differentiation may have a worse prognosis than those with poor differentiation, indicating the limitation of these markers in evaluating EC prognosis. Apparently, it would be much desirable to determine the key molecular events involved in cancer metastasis and invasion, which may shed light on selscting biomarker for prognosis and targeting therapeutic point and direction for metastasis and invasion.Rencent studies by us and other laboratory have showed that some molecular markers are related with EC prognosis. In fact, there may be multiple genes involved in EC invasion and metastasis, many factors may affect EC prognosis. Metastasis is regulated by cell adhesion proteolysis, and angiogenesis. In molecule level, these biologic phenomena are concern with many genes, which play different roles in different pathophysiological process. Therefore, combining several biomarkers together may provide more accurate informations in predicting the prognosis.Survivin, VEGF and E-cad (E-cadherin), the three markers are significant correlated with tumor invasion and metastasis process. But there are few reports on their expression in EC and their correlation to EC prognosis in the high incidence area in Henan. The present study was thus undertaken to follow up esophageal carcinoma patients from the high-incidence area, and to determine the alternations of these three markers and prognosis with the EC using histopathological and immunohistochemical methods. Combining clinical informations with different molecular changes, esophageal carcinoma patients' survival risk was analyzed, to provide the theoretical basis and strategies for clinical biotherapy and preventions, and furtherly to explain the mechanism of invasion and metastasis. Furthermore, these three biologic molecular markers were compared together with P53, PCNA and MUC1, which might establish a prognosis evaluating model.Materials and MethodsOne hundred and fourteen patients with 66 men and 48 women, who had undergone esophagectomy at the Esophageal Carcinoma Hospital of Linzhou City between 1993 and 1996, were enrolled in this study. All the patients had not received radiation therapy or chemotherapy before surgery. The mean age was 53.5 8.1 years for males and 53.6 7.8 years for females, and the age range was 37-72 in males and 40-69 in females, respectively. All the patients were local residents of Linzhou city, and were followed up after surgery until March 2001, at which the patients had survived more than 5 years or died within 5 years after surgical treatment. 57 patients who survivedless than 5 years were all died of recurrence or metastasis, without other serious diseases, accident and obvious causation. All tumor samples were fixed with formalin and embedded with paraffin. Each block was sectioned serially at 5 urn, one was stained with hematoxylin and eosin for histopathological analysis by two pathologists and the others were used for immunostaining (ABC). The cumulative survival...