Expression Of Tumor Necrosis Factor-alpha-induced Protein8in Pancreas Tissue And Its Correlation With Epithelial Growth Factor Receptor Levels

Background and objective:Pancreatic cancer (PC) is a high degree of malignant gastrointestinal tumors, accounting for common malignant tumor of1%-2%. Its incidence varies among the area, higher in the developed countries and the industrialized countries, lower in the African and Asian countries. In recent years, along with the improvement of living standard and the increasing medical examination of the technology, and the diagnosis of pancreatic cancer in our country increased year by year. According to the Statistics from Beijing, Shanghai, Tianjin, pancreatic cancer is the10th for the mortality of patients with cancer ten years ago, however in recent years it rose to fifth and has become one of the ten death causes of population. Pancreatic cancer is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Analysis of overall survival shows that the prognosis of PC is still quite poor despite the fact that1-year survival and5-years survival have increased over the years. Its precipitating factors are drinking, Diabetic Mellitus, smoking, chronic pancreatitis and Genetic predisposition. As we all know, the development of cancer is a complicated process, its mechanism and related research is not clear yet. It’s found that in tumor tissue there are often high expression of oncogene and low expression of tumor suppressor gene. Tumor necrosis factor (TNF)-alpha-induced protein8(TNFAIP8or TIPE) is recently identified protein which is considered to be associated with carcinogenesis, alias:GG2-1; SCCS2; SCC-S2; MDC-3.13, encoded by gene TNFAIP8. Since it was found, many studies show that TNFAIP8express high level in breast, prostate, lung cancer tissues, and further studies show that in vitro it promotes the growth of cancer and migration. However, the research about the correlation of protein TNFAIP8and pancreatic cancer doesn’t exit. The aim of the experiment is to explore the expression pattern of TNFAIP8protein in pancreatic cancer tissues and to analyze its correlation with clinic pathological significance and the expression levels of EGFR. Immunohistochemistry was performed to detect the TNFAIP8protein and EGFR in pancreatic cancers, pancreatitis tissues, and health controls.Material and method:This study was conducted with the approval of the Fundamental Laboratory of provincial hospital affiliated to Shandong University, China. Pancreas tissues were obtained from78patients (Male42,Female36), of pancreatic cancer56patients(well differentiated14, moderately differentiated21, poorly differentiated23) who underwent complete resection in provincial hospital affiliated to Shandong University between2003and2010, and normal pancreatic tissues12patients, Chronic pancreatitis tissues10patients. Follow up information was obtained from review of the patients medical records. None of the patients had received radiotherapy or chemotherapy before surgical resection, and all of them were treated routine chemotherapy after operation. The mean age of the patients was53.5years (rang35-65years old). The histological diagnosis and grade of the differentiation were evaluated using hematoxylin-eosin-stained sections according to the World Health Organization Guidelines of Classification. All56specimens were revaluated with respect to histological subtype, differentiation and tumor stage. The lymph node metastases were identified in13of the56pancreatic cancer patients. The TNM staging system of Union for International Cancer Control was used to classify specimens. immunohistochemistry was performed to detect the TNFAIP8protein and EGFR in pancreatic cancers, pancreatitis tissues, and health controls. Results:1. The expression of TNFAIP8and EGFR in pancreatic cancer:The expression of TNFAIP8was mainly located in the cytoplasm of pancreatic cancer cells and normal pancreatic cells, and there was no expression in the nucleus. There was negative expression in most of the normal pancreatic cells. The expression level of TNFAIP8in pancreatic cancer tissues was0.12562±0.0711, significantly higher than that in the normal pancreatic tissues0.01832±0.0099(P<0.01), however its expression level in chronic pancreatitis is high0.25153±0.0815. The positive expression of EGFR was mainly located in cytoplasm of pancreatic cancer cells, and there was no expression in the nucleus.2. Through the analysis of relationship between the TNFAIP8expression in pancreatic cancer tissue and its clinical pathology characteristic, such as the patient’s gender, pancreatic cancer differentiation, TNM stage and local lymph node metastasis, we found there was no significant correlation between TNFAIP8expression and gender. But the expression of the TNFAIP8was correlated with pancreatic cancer differentiation, TNM stage and local lymph node metastasis (P<0.05). In other words, patients with low TNM stage and local lymph node metastasis had more expression of TNFAIP8than the ones with high TNM stage and no lymph node metastasis.3. Through the analysis of relationship between TNFAIP8expression and EGFR expression, there was the strong positive correlation (r=0.671135,.P<0.05) between TNFAIP8and EGFR expression, and in a series of pancreatic cancer tissue sections, the positive staining area of TNFAIP8expression was consistent with that of EGFR expression. Always the slides with high TNFAIP8expression had more EGFR expression.Conclusions:1. The high expression of the TNFAIP8is correlated with pancreatic cancer differentiation, TNM stage and local lymph node metastasis, which suggests that TNFAIP8may promote the progress and metastasis of pancreatic cancer by Promoting cell proliferation.2. Our results show that there is strong positive correlation between TNFAIP8and EGFR expression, which indicates TNFAIP8may increase the expression of EGFR and promote the growth and metastasis of pancreatic cancer through up-regulation of EGFR expression.3. According to our results, TNFAIP8expression in Chronic pancreatitis tissues is high too, we infer the proliferation of mass inflammatory cells and other cells in the tissue may account for it. Tumor necrosis factor (TNF)-alpha-induced protein8(TNFAIP8or TIPE) is recently identified protein which is considered to be associated with carcinogenesis. To investigate the expression pattern of TNFAIP8protein in pancreatic cancer patients and to analyse its correlation with clinicopathological significance and the expression levels of EGFR, immunohistochemistry was performed to detect the TNFAIP8protein and EGFR in pancreatic cancers, pancreatitis tissues, and health controls. The results showed that a stronger staining of TNFAIP8protein was detected in pancreatic cancer tissues compared with normal pancreas tissue. Furthermore, in56patients with pancreatic cancer, the expression levels of TNFAIP8in patients with low Tumor stage is higher than that with high Tumor stage, and the excessive expression of TNFAIP8is correlated with tumor staging and lymph node metastasis (P<0.05), and TNFAIP8expression positively correlated to EGFR (r=0.671135, P<0.05).These results indicate that TNFAIP8may play a important roles in the progression of pancreatic cancer.