Expression Of Autophagy-related Gene Beclin1 And PTEN In Esophageal Squamous Cell Carcinoma

The incidence of esophageal carcinoma is higher in China than that in other countries, and while the mortality of esophageal carcinoma is the highest all of the word. Esophageal carcinoma is a serious threat to people's health in our country. Therefore, how to conduct the early diagnosis of esophageal carcinoma and the chemical therapy of the esophageal carcinoma at its late stage becomes a major problem to be solved by clinical doctors. The study on the pathogenesis of esophageal carcinoma may provide a theoretical basis for the early diagnosis and treatment of esophageal carcinoma. At present, it has become special focus to investigate the oncogensis, developing, metastasis and management of the tumor from the molecule level. It is normal that the cell is in the balance of proliferation and death, the tumor cells is unlimited proliferation. The tumor and the cell death are strictly related. Therefore, the study on the death of tumor cells becomes a key to research on tumors. There are three forms of cell death, autophagy, apoptosis, and necrosis. Apoptosis is a caspase-mediated programmed cell death with apoptotic body as its characteristic, also known type I cell death. Autophagy is a non-caspase-mediated programmed cell death with autophagosome as its characteristic, known as typeⅡcell death. Recent studies have been shown that the change in autophagic activity is related to the development of malignant tumors. Autophagy is a biological process strictly regulated by a series of genes. Autophagy-related gene Beclinl and PTEN are key genes in the regulation of autophagosome formation. therefore, they are very close relationship with the tumor. Beclinl can promote autophagy capacity through the ROS pathway. Studies have been shown that the lack of heterozygosity is one of the causes of the malignant transformation of cells. Beclinl is a possibly a tumor suppressor gene. PTEN is a phosphatase gene, can promote autophagic capacity by reducing the concentration of PI3K kinase. PTEN plays a role of tumor suppressor genes by promoting autophagic capacity. Therefore, the study on the expressions of Becinl and PTEN in esophageal carcinoma can offer biological basis for the diagnosis and therapy of esophageal carcinoma and provide the development of new drugs with theoretical basis.To investigate the expressions of autophagy-related gene Beclinl and PTEN in esophageal squamous cell carcinoma, and their relationships between their expressions and clinical pathological features and clinical significance.66 patients with 48 males and 18 females who had undergone esophagectomy in the department of Pathology, The First Affiliated Hospital of Zhengzhou University in 2007, were enrolled in this study. The range of ages were 34-75 years.The average ages were 58.0±11.2 years. Esophageal squamous cell carcinoma had been proved by histopathological diagnosis in all tissue samples,34 well-differentiated and 32 moderately and poorly differentiated; 32 below deep muscular layer and 34 above deep muscular layer; 33 with lymph node metastasis and 33 without lymph node metastasis. All patients had not received radiation therapy and/or chemotherapy before surgical treatment. All tumor samples were fixed with 10% formalin and embedded with paraffin. Each block was sectioned serially at 4μm, one was stained with hematoxylin and erosion for histopathological analysis by two pathologists and the others were used for immunostaining. Blades were removaled endogenous hydrogen peroxidase with liquor hydrogen dioxide whose concentration was 3% after deparaffinage and hydration, recovering antigen with microwave, then progressing the rest procedures according to the instruction of kit, the dilutions of antibodies both were 1:100. To do positive control with positive blade and negative control with phosphate buffered solution(PBS). The dates were analyzed by statistical software SPSS 10.0:Chi-squared test and Spearman's rank correlation were performed to compare difference between samples and relativity analysis respectively. The significant difference was considered when the P value was less than 0.05.1 Beclinl and PTEN protein express positively in cell cytoplasm of esophageal squamous cell carcinoma and normal tissues.2 The positive ratio of Beclinl protein which was 48.5%(32/66) in esophageal squamous cell carcinoma was lower significantly than that in normal tissues which was 89.5%(34/38) (P< 0.05). The positive ratio of Beclinl in well-differentiated samples 82.4%(28/34) was significantly higher than that moderately and poorly differentiated samples 12.5%(4/32) (P< 0.05). It was not observed that the positive ratio of Beclinl was related to the depth of carcinoma tissue infiltration and lymph node metastasis (P>0.05). 3 The positive ratio of PTEN protein which was 45.5%(30/66) in esophageal squamous cell carcinoma was lower significantly than that in normal tissues which was 94.7%(36/38) (P<0.05). The positive ratio of PTEN in well-differentiated samples 76.5%(26/34) was significantly higher than that in moderately and poorly differentiated samples 12.5%(4/32) (P<0.05). The positive ratio of PTEN in below deep muscular layer samples 68.7%(22/32) was significantly higher than that in above deep muscular layer samples 23.5%(8/34) (P<0.05).The positive ratio of PTEN in without lymph node metastasis samples 6.7%(22/33) was significantly higher than that in lymph node metastasis samples 24.2%(8/33) (P< 0.05).4 The expression of Beclinl in esophageal squamous cell carcinoma was positively related to expression of PTEN(rs=0.754,P<0.05).1 The expressions of Beclinl and PTEN are down-regulated in esophageal squamous cell carcinoma, and they are associated with tumor cell differentiation. The change of autophagic capacity may be related to the emergence and development of esophageal squamous cell carcinoma.2 Expression of Beclinl and PTEN show obvious positive correlation in esophageal squamous cell carcinoma. It suggests that the cooperative expression of them has the same modulatory mechanism.