| Background:With the highest fatality ratio, malignant tumor is the leading cause of death in human diseases. Although the diagnosis and treatment of malignancy has been developed to a much more advanced level during the past decades, it is still a tough problem which has not been conquered in the current medical circles. Periampullary carcinoma is a collective term used for cancers arising from or near the ampulla of Vater and include ampullary carcinoma, pancreatic head cancer, distal cholangiocarcinoma and duodenal cancer. Periampullary cancers are the third most frequent gastrointestinal tumors following gastric and colorectal cancers. These tumors exhibit similar symptoms, but different clinical outcomes, according to their anatomic origin. The exact site of origin of periampullary tumors is often difficult to ascertain preoperatively. Ampullary carcinoma, defined as a tumor grossly appearing to arise in the ampulla of Vater. Three epithelial types can be involved in this area: those arising from the bile duct, the pancreatic duct, or the duodenal mucosa. Ampullary carcinoma is a relatively uncommon neoplasm. It accounts for approximately0.2%of all tumors in the gastrointestinal tract and constitutes about7to20%of the periampullary neoplasms, being the second most frequent tumor of this region.The first resection for a periampullary carcinoma was performed by the German surgeon Kausch in1912. It is often called the Whipple procedure, after the American surgeon Whipple who devised an improved version of the surgery in1935. Reconstruction consists of attaching the pancreas to the jejunum and attaching the hepatic duct to the jejunum to allow digestive juices and bile respectively to flow into the gastrointestinal tract and attaching the stomach to the jejunum to allow food to pass through. Whipple originally used the sequence:bile duct, pancreas and stomach, whereas presently the popular method of reconstruction is pancreas, bile duct and stomach, also known as Child’s operation. Regardless of the site of origin of these tumors, most patients undergo a similar operative procedure for extirpation of their disease:radical pancreaticoduodenectomy. Because even small lesions in the ampulla can obstruct the bile duct, early jaundice and early presentation occurs, which may lead to early dignosis and high resectability rate. Pancreatoduodenectomy is the main treatment of choice for tumors of the ampulla of Vater. Local procedures such as simple ampullectomy has been proposed to obviously reduce operative complication and mortality. The overall five-year survival of25%to67%. Many patients will still experience a regional recurrence and metastasis. There is a need for a better understanding of the pathologic mechanism of ampullary carcinoma, the identification of potential prognostic factors, and clinically relevant molecular targets for therapy.Modern medical studies have showen that the formation and development of malignant tumors are not only associated with abnormal proliferation and differentiation, but also involved in inhibition of apoptosis which was one of the important mechanisms in the forming of tumors. So, apoptosis and tumor became a hot focus in tumor molecular biological researches.Livin is a member of the inhibitors of apoptosis (IAP) family. Livin gene spans4.6kb on chromosome20at band q13, and including six introns and seven exons. Livin protein contains a single BIR domain and a RING linger motif. Livin gene has two splice variants:Livin α and β, which are almost identical. Conceptual translation indicates that Livin a and P are almost identical proteins that share the amino-terminal BIR and carboxyterminal RING domains. The two cDNAs contain open reading frames of298and280amino acids. With the exception of the placenta, heart, lung, spleen and ovary, the messenger RNA(mRNA) for Livin is not detectable in most normal adult tissues. However, it is detectable in fetal tissues (brain, kidney,heart and spleen) and is overexpressed by some cancer cells. Livin is presented in several cancer tissures, such as melanoma, leukemia, lung cancer cells, bladder cancer, prostate cancer, gastric cancer, colon cancer, hepatocelluar carcinoma and pancreatic cancer. Livin plays critical role in apoptosis inhibition, regulating the cell cycle, participating in tumor angiogenesis and anti-nature killer cells action. The majority of the current datas suggest that Livin expression in cancer appears to be associated with unfavorable clinico-pathological parameters, such as disease relapse and shorter patient survival. It has close relation with the occurence of tumors. Livin served as a new target for apoptosis-inducing therapy of malignant tumors.Caspase family is a class of amino acid sequence, spatial structure and substrate specificity are similar specificity of aspartic acid-cysteine protease. The occurence of apoptosis is a complex, mediated by the Caspase family members of the protease cascade process, but the district is located downstream effector. Caspases, are the key effectors of the cellular death. Among the caspases, Caspase-3(also known as CPP32, YAMA) is probably the one that so far best correlates with apoptosis. Caspase-3activation was considered to be the only way cascade. Livin mainly through its BIR district and cysteine aspartate-specific proteases(Caspases) combination of direct inhibition of cysteine protease caspases, in particular, inhibit Caspase-3,7and9activity, to resistance fault-related apoptosis receptor and mitochondrial apoptosis pathway, while the realization of the inhibition of apoptosis. Ki67is a nuclear antigen expressed mainly in the S and M phases of the cell cycle, and it has been used in many studies for estimating the growth fraction of various tumor types.Inspite of elemantary study on Livin has been made, the specific mechanism of action in ampullary carcinoma is still unknow, which deserves further research. In this study we investigated expression of Livin, Caspase-3and ki67in ampullary carcinoma and its relation of sex, tumor size, histological type, tumor differentiation, TNM stage, CA19-9and lymph node metastasis, analysied the relation of livin with Caspase-3and ki67expression, so as to preliminarily inestigate the facilitaion mechanism of livin about tumor growth, to better understand the process of cell muliplication, proliferation, apoptotis in ampullary carcinoma, to further comprehend the role that Livin palys in the development and progression and ultimatly to provide more theoretical evidences for the treatment and prognostic judgement of ampullary carcinoma.This experiment is to study the expression of Livin, Caspase-3and ki67in ampullary carcinoma, and explore Livin, Caspase-3and ki67expression in the relationship correlations with clinicopathologic features and prognosis by exploring the relation between Livin overexpression and Caspase-3in it, and finally discussed the potential significance to determine whether the level of Livin expression could predict poor prognosis of patients with ampullary carcinoma.Objective To investigate the expressions of Livin, Caspase-3and ki67and their correlations with clinicopathologic charactistics and prognosis in patients with ampullary carcinoma.MethodsThe expressions of Livin, Caspase-3and ki67were analyzed by immunohistochemistry using the streptavidin peroxidase complex method for71patients with ampullary carcinoma after surgery, and then their correlations with clinicopathologic charactistics were investigated. Meanwhile, we retrospectively analyzed the relationships between them with the survival time of the patients.ResultsOf the71patients with ampullary carcinoma, the accuracy rate of diagnosis with colour doppler ultrasound, CT, MRCP and ERCP was70.4%(50/71),85.9%(61/71),91.3%(42/46) and91.6%(11/12) respectively. There was a significant difference between colour doppler ultrasound and CT, MRCP (P<0.05). There was not significant difference among CT, MRCP, ERCP(P>0.05). Immunohistochemistrical results showed that the positive expressions of Livin, Caspase-3and ki67in ampullary carcinoma were46.5%(33/71),54.9%(39/71) and56.3%(40/71) respectively. The positive expressions of Livin, Caspase-3and ki67in paracancerous tissues were O(?)(0/52).75%(39/52) and25%(13/52) respectively. A very significant difference was found in the expression of Livin. Caspase-3and ki67protein between cancer tissues and paracancerous tissues (all P<0.05). The positive expression of Livin was associated with tumor differentiation, tumor-node-metastasis (TNM) stage, and lymph node metastasis (P<0.05), rather than of age, sex, tumor size, histological type, and CA19-9(P>0.05). The expression of Caspase-3and ki67were both significantly associated with tumor differentiation (P<0.05). but not with other clinicopathological features (all P>0.05). There was a significant negative correlation between Livin and Caspase-3(r=-0.575, P<0.001), and a positive correlation between Livin and ki67(r=0.308, P=0.009). Survival analysis showed that positive Livin expression group had a significantly poorer overall survival rate than negative Livin expression group did (P<0.05). Multivariate analysis demonstrated that Livin expression and lymph node metastasis were independent prognostic factor in ampullary carcinoma.Conclusion The positive expression rates of Livin protein were higher in ampullary carcinoma than in paracancerous tissues. It suggested that Livin protein expression was related in the development and progression of ampullary carcinoma. The expression of Livin was negatively correlated with Caspase-3, but positively correlated with ki67in ampullary carcinoma, suggesting that Livin probably inhibit Caspase-3activation directly or indirectly to protect cells apoptosis from occurring resulting in the occurring and procession of ampullary carcinoma. Livin is a valuable prognostic factor for ampullary carcinoma. Meanwhile, the current study indicates that Livin may have an important role by inhibiting apoptosis during the progress of ampullary carcinoma. |
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