ABSTRACT
Objective To investigate the significance of Thyroid hormone receptor interactor 6 (TRIP6) in the development of pancreatic cancer.Methods The protein expression of TRIP6 was assessed immunohistochemically in 43 normal pancreatic (NP) tissues,18 pancreatic intraepithelial neoplasia (PanIN)tissues and 50 pancreatic ductal adenocarcinoma (PDAC) tissues using the immunohistochemical scores (IHCS) to evaluate the positivity of TRIP6 expression.And the expression of TRIP6 in different tissues was analyzed,and the correlations of TRIP6 expression in PDAC tissue with clinicopathological characteristics were analyzed.Results TRIP expression was negative or extremely low in normal pancreas,which changed from weak positivity to strong positivity with the increased degree of tissue atypia.TRIP6 was strongly expressed in PDAC.The IHCS of TRIP6 expression in NP,PanIN-1,PanIN-2,PanlN-3 and PDAC was(0.010 ±0.003),(0.029 ± 0.003),(0.055 ± 0.014),(0.090 ± 0.025) and (0.094 ± 0.030),and the differences were statistically significant (P ＜0.01).The results of paired comparison of either two of them above showed that the expression of TRIP6 in NP group was significantly lower than that in other four groups,the expression in PanIN-1 group was significantly lower than that in other three groups except NP group,the expression of PanIN-2 group was significantly lower than that of PanIN-3 group and PDAC group,and all the differences were statistically significant (all P ＜ 0.05).However,the expression of PanIN-3 group was lower than that of the PDAC group,but the difference was not statistically significant (P =0.13).The expression level of TRIP6 was associated with neural invasion (P＜0.01),lymph node metastasis (P=0.013),distant metastasis (P=0.018),differentiation of PDAC (P=0.019) and CA19-9 level(P＜0.01) in PDAC,but not with patients' gender,age,tumor size,location,vascular infiltration,infiltration depth and TNM stage.Conclusions Overexpression of TRIP6 is an early event in PDAC.TRIP6 may be involved in the whole process of PDAC development and progression.
ABSTRACT
Objective To observe the expression of Wnt5a protein in different pancreatic tissues and to evaluate the role of Wnt5a in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC), so as to provide new clues for the diagnosis and treatment of pancreatic cancer. Methods Immunohistochemical SP method was used to examine the expressions of Wnt5a protein in 21 normal pancreatic duct tissues, 73 pancreatic intraepithelial neoplasia(PanIN)-l tissues, 29 PanIN-2, 16 PanIN-3 tissues, 20 intraductal papillary mucinous neoplasm (IPMN) adenoma (IPMA) tissues, 13 IPMN-borderline (IPMB) tissues, 19 IPMN-carcinoma (IPMC) tissues and 50 PDAC tissues. The correlation of Wnt5a expression with clinicopathologic characteristics and postoperative survival of PDAC patients was analyzed. Results Wnt5a expression increased with the progression of the lesions in the following order: NP(0)-»PanIN-l(l. 90 ± 1. 192)»PanIN-2(3. 03 ± 1. 322)»PanIN-3(4. 88 ± 1.455) or NP(0)-»IPMA(1. 40 ± 0. 940)-»IPMB (2. 62 ± 1. 502)»IPMC (3. 00 ± 1. 374), and PDAC(3. 11 ± 2. 635). Wnt5a expression was significantly correlated with tumor proliferation activity, distant metastasis, TNM staging and postoperative survival (P<0. 05). The median survival periods of PDAC patients with high and low Wnt5 expression were 15 months and 21 months, respectively(P = 0. 015). Conclusion Wnt5a is involved in the development and progression of PDAC. Enhancement of Wnt5a expression is an early event in PDAC; sustained or over-expression of Wnt5a may affect the proliferation, invasion and metastases of pancreatic cancer cells, and may indicate a poor prognosis.
ABSTRACT
Animal models of pancreatic cancer are important for the experiments of pancreatic cancer research. An ideal animal model of pancreatic cancer provides effective tool for exploring the tumorigenesis of pancreatic cancer. This paper summarizes the methods for establishing mouse model of pancreatic ductal adenocarcinoma and discusses interpretd the advantages and disadvantages of different models.
ABSTRACT
Pancreatic intraepithelial neoplasia (PanIN) is a precancerous lesion. A 72-year old man was admitted to our hospital because of abdominal pain, and he had an elevated serum level of pancreatic amylase. ERCP showed a focal stricture of the main pancreatic duct without upstream dilatation in the body of the pancreas. Cytologic evaluation with an endoscopic brush at the stricture suggested the presence of adenocarcinoma. After subtotal pancreatectomy, the features of PanIN were observed in the branch pancreatic duct. ERCP with brush cytology seems to be a useful method for detecting PanIN at the precancerous stage. We report here on a case of PanIN associated with a stricture of the main pancreatic duct.
Subject(s)
Abdominal Pain , Adenocarcinoma , Amylases , Cholangiopancreatography, Endoscopic Retrograde , Constriction, Pathologic , Dilatation , Pancreas , Pancreatectomy , Pancreatic Ducts , PancreatitisABSTRACT
Background and purpose: Pancreatic intraepithelial neoplasia (PanIN) is thought to be a precursor lesion of infiltrating pancreatic ductal adenocarcinoma. The mutation of the phenotypic impact of K-ras G12D alone, silencing of p53 and p16 could promote this process. The role of Smad4 in this progression was poorly understood. In the present study, we investigated the role of Smad4 in the development of pancreatic tumor, based on PanIN cell line from mice with K-ras G12D mutation in order to investigate the effect of Smad4 silencing on PanIN cells in the development and malignant transformation in nude mice. Methods: Smad4 knock-down PanIN cells (PanIN-S) were established by stable transfeetion with lentiviral-mediated Smad4 RNA interference (RNAi). In xenograft model experiments, BALB/c nude mice were randomly divided into 2 groups (5 mice per group) implanted with PanIN or PanlN-S cells subcutaneously. Two weeks after tumor cells inoculation, tumor volume and weight were estimated. PCNA staining was used to evaluate cell proliferation and CD31 polyclonal antibody was used to assess micro-vessel density (MVD) in tumors. Results: Effect of siRNA of Smad4 gene in PanlN cells was confirmed by RT-PCR and Western blot. Compared with PanlN groups, there was a dramatic increase in tumor volume and weight in PanIN-S groups (P<0.05). Furthermore, immunohistochemical analysis of the harvested tumors suggested that Smad4 silencing was associated with 'increased tumor cell proliferation (PCNA reactivity) and angiogenesis (micro-vessel density, MVD). The percentage of PCNA-positive cells in the PanlN-S groups were significantly increased than PanIN groups (P<0.05). CD31 staining revealed a significant increase in the PanlN-S groups compared to the PanlN groups (P<0.05). Conclusion: Silencing of Smad4 in PanlN cells with endogenous expression of K-ras G12D, enhanced progression to invasive adenocarcinomas. Cell proliferation and vascularization may be its important mechanisms.
ABSTRACT
Objective To investigate the appropriate method in diagnosing precursor lesions of pancreatic cancer and its treatment. Methods From Jan. 2006 to Dec. 2007, 92 cases were operated for pancreatic neoplasms. Among them 7 cases had pancreatic precursors. The mucinous cystic neoplasm was found in 1 case, intraductal papillary mucinous neoplasm(IPMN) in 2 cases, endocrine tumor in 1 case and pancreatic intraepithelial neoplasia (PanIN) in 3 cases. CA19-9 level was tested by immunoflucence assay. All of the 7 patients were examined by CT. Endoscopic ultrasound(EUS) and endoscopic retrograde cholangio-pancreatography examinations were performed on 1 and 2 patients respectively. Results There was neither specific symptom related to these precursors nor any evidence of mass as revealed by CT or ultrasound. But dilatation and stricture of pancreatic duct were found in PanIN patients, and cystic dilatation of pancreatic duct in pancreatic head was present more in IPMN patients. For cystic neoplasms in pancreatic body and tail, they were commonly solid and isolated. CA19-9 level was slightly elevated in some patients but with no diagnostic value. Surgical resection was done with excellent result. Conclusion For the suspected pancreatic precursors, aggressive diagnostic approach and surgical resection will be the best option and can further prevent cancer development.
ABSTRACT
This review article describes morphological aspects, gene abnormalities, and mucin expression profiles in precursor lesions such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) of the pancreas, as well as their relation to pancreatic ductal adenocarcinoma (PDAC). The gene abnormalities in precursors of PDAC are summarized as follows: (1) KRAS mutation and p16/CDKN2A inactivation are early events whose frequencies increase with the dysplasia grade in both PanIN and IPMN; (2) TP53 mutation and SMAD4/DPC4 inactivation are late events observed in PanIN3 or carcinomatous change of IPMN in both PanIN and IPMN, although the frequency of the TP53 mutation is lower in IPMN than in PDAC; and (3) also in MCN, KRAS mutation is an early event whose frequency increases with the dysplasia grade, whereas TP53 mutation and SMAD4/DPC4 inactivation are evident only in the carcinoma. The mucin expression profiles in precursors of PDAC are summarized as follows: (1) MUC1 expression increases with the PanIN grade, and is high in PDAC; (2) the expression pattern of MUC2 differs markedly between the major subtypes of IPMN with different malignancy potentials (i.e., IPMN-intestinal type with MUC2+ expression and IPMN-gastric type with MUC2- expression); (3) MUC2 is not expressed in any grade of PanINs, which is useful for differentiating PanIN from intestinal-type IPMN; (4) de novo expression of MUC4, which appears to increase with the dysplasia grade; and (5) high de novo expression of MUC5AC in all grades of PanINs, all types of IPMN, MCN, and PDAC.
Subject(s)
Adenocarcinoma , Mucins , Pancreas , Pancreatic Ducts , Pancreatic NeoplasmsABSTRACT
Animal models of pancreatic cancer are important for the experiments of pancreatic cancer research.An ideal an- imal model of pancreatic cancer provides effective tool for exploring the tumorigenesis of pancreatic cancer.This paper summari- zes the methods for establishing mouse model of pancreatic ductal adenocarcinoma and discusses interpretd the advantages and disadvantages of different models.