Objective: To study the relationship between epithelial-mesenchymal transition (EMT) phenotype of circulating tumor cells (CTCs) and liver metastasis of pancreatic cancer.Methods: The patients who were found without liver metastasis by preoperative imaging examination but confirmed with pancreatic cancer by postoperative pathological diagnosis were recruited in this study from January 2010 to December 2013 in Department of General Surgery, Changzheng Hospital, Second Military Medical University. All patients were followed up for 1 year after surgical operation, then divided into liver metastasis group and non-liver metastasis group according to whether the patient had liver metastasis or not during the follow-up. In each group, 50 patients were randomly selected. The peripheral blood samples from all patients were collected before surgery, and at the same time, the peripheral blood samples from 10 healthy volunteers were collected as the control. Then the CTCs were enriched and isolated from peripheral blood samples using immunomagnetic method, and identified by immunofluorescence method with carbamoyl-phosphate synthetase 1 (CPS1) antibody. The expressions of EMT markers Snail and Vimentin in blood samples were detected by immunofluorescence method. The relationships between these EMT markers and liver metastasis of pancreatic cancer were analyzed by univariate and multivariate analyses.Results: CPS1, Snail and Vimentin were not expressed in blood samples from 10 healthy volunteers. In peripheral blood samples from 50 pancreatic cancer patients with liver metastasis, the positive expression rates of Snail and Vimentin were 82% (41) and 72% (36), respectively; while in non-liver metastasis group, the positive expression rates of Snail and Vimentin were 20% (10) and 12% (6), respectively. The positive expression rates of Snail and Vimentin in liver metastasis group were higher than those in non-liver metastasis group (χ2 = 38.455, P 37 kU/L, tumor diameter ≥ 4 cm, pancreatic head tumors, vascular invasion, and positive expressions of Snail and Vimentin were correlated with liver metastasis of pancreatic cancer (all P 37 kU/L (β = 3.411, P < 0.01) and positive expressions of Snail (β = 2.882, P < 0.01) and Vimentin (β = 3.361, P < 0.01) were independent risk factors for liver metastasis of pancreatic cancer.Conclusion: CTCs-EMT phenotype markers Snail and Vimentin in peripheral blood may be closely related to liver metastasis of pancreatic cancer. DOI:10.3781/j.issn.1000-7431.2015.33.221
Objective To analyze the differential expression and clinical significance of mucin 4 ( MUC4) in pancreatic in-traepithelial neoplasias (PanINs) and pancreatic ductal adenocarcinoma (PDAC). Methods We collected 85 cases of paraffin of pancreatic tissue specimens from Affiliated Changzheng Hospital of the Second Military Medical University from 2009-03-01 to 2011-12-31. Immunohistochemical SP method was used to examine the expression of MUC4 in 48 normal pancreatic duct (NP) tissues, 17 Pan-INs tissues and 20 PDAC tissues. The correlation of MUC4 expression with clinicopathological characteristics and prognosis of PDAC patients was analyzed. Results MUC4 was not expressed in NP;MUC4 expression gradually increased with the progression of pancre-atic tissue. The positive expression rates of MUC4 in NP, PanIN-1, PanIN-2, PanIN-3 and PDAC were 0, 17. 4%, 52. 6%, 84. 6%and 90. 0%, respectively; The immunohistochemical scores of MUC4 expression in NP, PanIN-1, PanIN-2, PanIN-3 and PDAC groups were 0, 1. 30±0. 89, 2. 58±1. 76, 4. 54±1. 64 and 7. 68±2. 34, with statistic significance among groups (P<0. 001). The ex-pression level of MUC4 was associated with neural invasion ( P=0. 028) , lymph node metastasis ( P=0. 020) and CA19-9 level ( P=0. 028) in PDAC. The median overall survival(OS) of PDAC patients was 17. 0 months(95%CI:14. 809-19. 191 months);The median OS of MUC4 high expression group ( immunohistochemical score≥8. 8) and low expression group ( immunohistochemical score <8. 8) were 13. 0 months ( 95%CI:7. 456-18. 544 months) and 20. 0 months ( 95%CI:15. 521-24. 479 months) , with statistic significance ( P=0. 003) . Conclusion MUC4 perhaps participates in the PDAC occurrence and development. MUC4 expression may be an early event in the evolution of PDAC. MUC4 high expression probably affects both invasion and metastasis of PDAC, and probably predicts poor prognosis.
Pancreatic cancer is a malignant with very poor prognosis.Although methods and technologies of diagnosis and treatment in connection with pancreatic cancer have made great progresses,the prognoses of patients with pancreatic cancer still have not a significant upgrade,which are closely related with the degree of malignancy of pancreatic cancer cells.Earlier studies have shown that normal pancreatic cells need to have a total of six capabilities,which are intimate connection with the degree of malignancy of pancreatic cancer cells,during the process of deterioration.A variety of immunohistochemical markers that correlate with prognosis of pancreatic cancer involve in the process of pancreatic cells obtaining these six capabilities.