Objective To investigate the expression of human trophoblast cell-surface antigen 2 (TROP2),phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2),and cyclin D1 in gallbladder carcinoma tissue and their correlation with clinicopathological parameters,as well as their association with the prognosis of patients with gallbladder carcinoma.Methods A total of 88 patients who were diagnosed with gallbladder carcinoma in Changzheng Hospital,Second Military Medical University,from June 2005 to June 2010 were enrolled,and their pathological specimens were obtained.Immunohistochemistry was used to measure the expression of TROP2,p-ERK1/2,and cyclin D1 in 88 gallbladder carcinoma tissue samples and 15 adjacent tissue samples.The chi-square test was used for comparison of categorical data between groups,and the Spearman method was used to investigate the correlation between any two parameters of TROP2,p-ERK1/2,and cyclin D1;univariate and multivariate Cox regression analyses were used to analyze the influencing factors for the prognosis of patients with gallbladder carcinoma;the Kaplan-Meier method was used to plot their survival curves.Results The positive rates of TROP2,p-ERK1/2,and cyclin D1 in gallbladder cancer tissue were 74.30%,58.40%,and 55.30%,respectively,significantly higher than those in adjacent tissue (5.42%,35.67% and 39.87%,respectively) (P < 0.05).The expression of TROP2,p-ERK1/2,and cyclin D1 was associated with gallstones,tumor diameter,degree of tumor differentiation,vascular and perineural invasion,lymph node metastasis,surgical procedure,and TNM stage (x2 =4.300 ~ 53.315,all P < 0.05).The expression of TROP2 was positively correlated with that of p-ERK1/2 and cyclin D1 (rs =0.402 and 0.742,both P < 0.001),and the expression of p-ERK1/2 was also positively correlated with that of cyclin D1 (rs =0.242,P =0.023).The multivariate survival analysis showed that positive expression of TROP2 had a significant influence on 3-year survival rate (RR =2.412,95% CI:1.186 ~5.126,P =0.010).Conclusion High expression of TROP2 may be an important reason for malignant progression of gallbladder carcinoma,and highly expressed TROP2 may mediate the high expression of p-ERK1/2 and cyclin D1,resulting in the malignant progression of gallbladder carcinoma.Positive expression of TROP2 is an independent risk factor for the prognosis of patients with gallbladder carcinoma and may be an effective target for clinical intervention.
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