Expression Of Paxillin And PTEN In Gastric Adenocarcinoma And Their Clinical Significance

AimsGastric cancer is one of the most common malignant tumors. The patients who died of gastric cancer occupy the first-position of all the malignant tumors, almost close to one quarter of the death toll of malignant tumors. Two million new gastric cancer patients would be founded each year. In recent years, the incidence of gastric cancer in the juvenile increase. But its early diagnosis, treatment and prognosis, are still not ideal, tumor cells'invasion and metastasis are the main factors that affect the prognosis and survival of patients. Paxillin is so far the only adherent and regulatory protein which combinates with oncogene and contains tyrosine, mainly located in the focal adhesion, and correlated with the formation of various tumors. PTEN (phosphatase and tensin homolog deleted on chromosome 10), also called MMAC1 or TEP1 gene, is found the only one tumor-suppressor gene which can make lipids-phosphorylated, its downregulation and deficiency is often related with a variety of advanced primary malignant tumors. Many research showed that Paxillin and PTEN might play important roles in the tumorigenesis, development, invasion and metastasis of many tumors, but their effects and related mechanisms with tumor are still unknown. The reports of joint detection the expression of Paxillin and PTEN in gastric cancer are rarely found. This experiment detects the expression of Paxillin and PTEN in normal gastric mucosa and gastric adenocarcinoma respectively, aims to judge the function of Paxillin and PTEN in the tumorigenesis, development, invasion and metastasis process of gastric adenocarcinoma, provide relevant evidence for patients to predict clinical prognosis, and choose appropriate adjuvant treatment.Materials and methods:88 patients with 64 males and 24 females who had undergone gastric adenocarcinoma in the department of pathology of the first affiliated hospital of Zhengzhou university between 2007 to 2008,were enrolled in this study. The range of age were 32～80 years. The average age was 58.5 years. Gastric adenocarcinoma had been confirmed by histopathological diagnosis in all tissue samples. TNM staging:Ⅰstage of 30 cases,Ⅱstage of 28 cases,Ⅲstage of 16 cases, and 14 cases ofⅣstage; 12 well-differentiated and 40 moderately and 36 poorly differentiated; 42 below subserosal layer and 46 above subserosal layer; 44 with lymph node metastasis and 44 without lymph node metastasis. Another 40 patients were taken from the normal patients with biopsy specimens of mucous membrane. All patients had not been received radiotherapy and/or chemotherapy before surgerical treatment. All tumor samples were fixed with 10% formalin and embeded with paraffin. Each block was sectioned serially at 4μm, some were stained with hematoxylin and erosin for histopathological analysis by two pathologists and the others were used for immunostaining. Blades were removed endogenous hydrogen peroxidase with liquor hydrogenii dioxidi whose concentration was 3% after deparaffinage and hydration, recoverying antigen with high-pressure, 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 datas were analysed by statistical software SPSS 11.0: Chi-squared test and Spearman's rank correlation were used to analyze the difference between groups, a=0.05 was considered as statistically significant value.Results1.Paxillin and PTEN expressed mainly in cell cytoplasm of cancer cells, Paxillin also had a cell membrane visible expression.2.The positive expression of Paxillin protein was 65.9% in gastric adenocarcinoma tissues was significantly higher than those in normal tissues which was 32.5% (P=0.000).Compared with well-differentiated and moderately-differentiated group, the positive ratio of poorly-differentiated group was significantly higher [53.8%(28/52) vs 83.3%(30/36)];Compared with below subserosal layer group, the positive ratio of above subserosal layer group was significantly higher [54.8%(23/42) vs 76.1%(35/46];Compared with without lymph node metastasis group, the positive ratio of lymph node metastasis group was significantly higher[54.5%(24/44) vs 77.3%(34/44)];Compared with TNM stagingⅠ～Ⅱstage group, the positive ratio of TNM stagingⅢ～Ⅳstage group was significantly higher[56.9%(33/58) vs 30.0%(9/30)].It was observed that the expressions of Paxillin were related to the differentiation, the invasion depth of gastric adenocarcinoma tissues, lymph node metastasis, and TNM staging (P>0.05).3.The positive expression of PTEN protein was 47.7% in gastric adenocarcinoma tissues was significantly lower than those in normal tissues which was 100% (P=0.000).Compared with well-differentiated and moderately-differentiated group, the positive ratio of poorly-differentiated group was significantly lower [61.5%(32/52) vs 27.8%(10/36)];Compared with below subserosal layer group, the positive ratio of above subserosal layer group was significantly lower[71.4%(30/42) vs 26.1%(12/46)];Compared with without lymph node metastasis group, the positive ratio of lymph node metastasis group was significantly lower [63.6%(28/44) vs 31.8%(14/44)];Compared with TNM stagingⅠ～Ⅱstage group, the positive ratio of TNM stagingⅢ～Ⅳstage group was significantly lower [56.9%(33/58) vs 30.0%(9/30)].It was observed that the expressions of PTEN were related to the differentiation, the invasion depth of gastric adenocarcinoma tissues, lymph node metastasis, and TNM staging (P>0.05).4. It was showed that there existed positive correlation between the expression of Paxillin and PTEN in gastric adenocarcinoma tissue (r=-0.369, P>0.05). Conclusions:1.The expressions of Paxillin were higher in gastric adenocarcinoma tissues than those in normal tissues. It indicated that the higher expression of Paxillin might relate to the occurrence of gastric adenocarcinoma.2.The result indicated that the overexpressions of Paxillin might relate with the differentiation, invasion depth, lymph node metastasis and TNM staging of gastric adenocarcinoma obviously. Overexpression of Paxillin indicated that cancer might have higher invasive and transfer ability. It can be used as a reference index to the degree of malignancy of gastric adenocarcinoma and prognosis.3.The expressions of PTEN in gastric adenocarcinoma tissues were significantly lower than those in normal tissues. The expressions of PTEN were related with of the differentiation, invasion depth, lymph node metastasis and TNM staging of gastric adenocarcinoma obviously. The results suggested that PTEN might be involved in the invasion and metastasis of gastric adenocarcinoma.4. Experssion of Paxillin and PTEN showed negative correlation in primary gastric adenocarcinoma. It suggested that the cooperative expression of them had the same modulatory mechanism.