Expression of trophoblast cell-surface antigen 2, phosphorylated extracellular signal-regulated kinase 1/2, and cyclin D1 in gallbladder carcinoma tissue and related clinical significance

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 (χ2=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.