The Expression Of Claudins In The Pancreatic Neuroendocrine Tumors

Pancreatic endocrine tumors (PETs) are rare neoplasms originating from the pancreatic islet cells,with a incidence of 0.5 per 100,000.And the majority are magliant except insulinoma.So it is very necessary to find some new markers helping to diagnosis and treat this tumors.In PUMCH,9 patients diagnosed as non-functional pancreatic endocrine tumors were collected ever since 2002.Among these patients, 4 cases had the liver metastasis and 5 cases were benign.There are 4 males and 5 females,ranging from 13 to 71 years old. The median age was 39 years old. 8 patients usually had no obvious symptoms, just diagnosed by medical examination. 1 case suffered from the epigastric discomfort.The five cases of benign tumors are single, with complete capsule of the mass. The size of tumors ranged from 1 to 6cm. For the four cases of cystic and one for the solid.The size of the 4 malignant tumors ranged from 1 to 15cm.And three cases of patients had adrenal gland and spleen involvement, lymph node metastasis and adipose tissue involevement around the pancrease.In addition, all patients had distant metastasis of liver, of which three cases of metastases confined to the right liver, a case for extensive liver metastasis.All of the 9 cases received the surgery treatment.2 cases of the benign tumors took the resection of the pancreatic body and tail. 1 patients received the body and tail of pancreas resection and splenectomy. 1 patients received laparoscopic pancreatic segment resection and the pancreas - stomach anastomosis. 1 case patients took the pancreaticoduodenectomy and cholecystectomy. All patients with good recovery and no severe postoperative complications. Of four cases of malignant tumor patients, 1 patients received the body and tail of pancreas radical resection ,splenectomy and liver metastasis resection; 1 patients received the body and tail of pancreas resection and splenectomy; 2 cases took the liver, abdominal wall metastasis resection.After operation,one patient suffered jaundice,another patient had pulmonary infection. Nine cases of postoperative patients were followed up for 4-60 months. Five cases of benign tumor were in good condition.1 patient died in the 23th month after the resection of iver, abdominal and lymph node metastases.1 case received liver metastases resection in the 14th month after operation,and in the 60th month ,the patient were in a poor condition. The other two patients were followed up until now, taking Chinese medicine treatment.Claudins was firstly found by Furuse from chicken liver in 1998.Together with occludin and JAMs,claudins consist of the tight junctions(TJs) between cells.What's more, claudins are proved to play the most important roles in the cell connections and tumor metastasis.On one hand,the down-regulation of the claudins make the number of TJs decrease,the connections between cells were destroyed ;on the other hand, although claudin protein expression are tissue-specific, claudin interactions between indifferent tissues can mediate xenogeneic cell-cell adhesion, involved in tumor distant metastasis. In this study, immunohistochemical staining was used to detect claudin-3, claudin-7 protein expression in the primary tumor and metastasis tissue. The experimental results confirmed that claudin-3,7 were positive in all the pathological specimens.In 6 cases of primary tumors and 4 cases of liver metastases samples, the expression of claudin-3 was positive.And claudin-7 protein was also detected in all the patients. Without enough amount of cases, we can not find the statistics differece between the benign and malignant tumors.In addition, there is no difference between liver metastasis and normal liver tissues in the expression of claudin-3, 7. The assumption of laudin-mediated cell heterogeneity adhesion remains to be confirmed in the follow-up experiment .Claudin proteins provided valuable clues in the search of tumor metastasis.Claudin-3, 4 are specific receptor of Clostridium perfringens exotoxin (CPE).Combine with the receptor , CPE can lead to cell necrosis.This experiment confirmed that claudin-3 protein expression were positive in the primary and metastatic lesions,which promise a valueable target for the treatment.Fully mechanized, in the last four decades, especially over the past decade, more and more studies have shown that claudin proteins directly or indirectly involved in the process of invasion and metastasis of tumor cells, and providing a new target for the pancreatic endocrine tumors diagnosis and treatment. However, claudins'role independent of the tight junctions,and interactions with the occludin , JAM proteins is still unclear, yet to be confirmed by further studies.