2020-08-012024-05-16https://scholars.lib.ntu.edu.tw/handle/123456789/666667Pancreatic cystic lesions are being increasingly detected with the widely used high resolution abdominal imaging, often an incidental finding. Pancreatic cystic tumors are precursors of pancreatic cancer. Pancreatic cancer is one of the most lethal cancers in human with poor survival. Difficulty in early detection of pancreatic cancer is a major factor related to the grave outcome. Appropriate management of these precursor lesions is an important way to interrupt progression to invasive cancers and thereby save lives4. Surgical of all noninvasive asymptomatic cystic lesions of the pancreas would be costly and associated with significant morbidity and mortality. Risk stratification for pancreatic cystic tumors is important to influence the clinical management. Current methods (clinical and radiological factors) of evaluating cystic pancreatic lesions are not satisfactory in differentiating the true histopathology and even more difficult to predict the presence of malignancy. The great challenge will be to detect these lesions before they progress to invasive cancer. To our knowledge, mutation of cationic trypsinogen gene (PRSS1) and cystic fibrosis transmenbrane reductance gene (CFTR) gene are reported to increase risks of pancreatic cancer in previous studies. Patients with PRSS1 mutation could habor hundreds (>100) times of risk of pancreatic cancer. Genetic factors associated with invasive pancreatic cancer might shed some light on risk stratification of pancreatic cystic tumor. Genetic factors associated with pancreatic cystic neoplasm are not known and reported before. The alterations of PRSS1 and CFTR (associated with traditional pancreatic cancer) in pancreatic cystic tumor and its association with malignant potential are never to be investigated. The carcinogenesis of pancreatic cystic tumor include oncogenic and tumor suppressive pathways. Among them , K-ras mutation is the most common reported one and might be activated in early stage of carcinogenesis. Cell cycle proteins, including p53, Rb, p16, DPC4, E2F1, Cyclin D1have been reported to be involved pancreatic ductal carcinoma with prognostic role. It is not known whether these cell cycle proteins are equally involved in the progression of pancreatic cystic tumors into invasive carcinomas. Furthermore, whether these genetic alterations have prognostic value in clinical settings is worthy to be studied. In the grant period, we will check the expression of these cell cycle proteins by using immunohistochemical staining in resected cystic pancreatic tumors tissues.We will check the K-ras mutation also. In addition, we will analyze methylation status of key tumor suppressor genes by methylation specific polymerase chain reaction (MSP) on genomic DNA from the resected tumors with correlation with the expression of RNA and protein. Based on these study, we might know more about the carcinogenesis in pancreatic cystic tumors. More importantly, we hope to find biomarkers for risk factors of malignancy and prognostic factors in pancreatic cystic neoplasm. The team led by the principal investigator represents a unique group successfully studying the molecular genetics also the first group taking the challenge of systemically investigating the cystic neoplasm of pancreas in Taiwan. Based on our previous experiences and compehensive data prospectively enrolled in this project, further studies will provide the most informative data on understanding the risks and prognostic factors in pancreatic cystic tumors.Pancreatic cystic tumorrisk factorprognostic factorgenetic alteration