Negative Expression of DSG1 and DSG2, as Prognostic Biomarkers, Impacts on the Overall Survival in Patients with Extrahepatic Cholangiocarcinoma.

Aims: To evaluate the expression of DSG1 and DSG2 and investigate their clinicopathological significance in EHCC.

Method: The protein expression of DSG1 and DSG2 was measured by EnVision immunohistochemistry in 15 normal biliary tract tissues, 10 biliary tract adenoma tissues, 30 peritumoral tissues, and 100 EHCC tumour tissues.

Result: The expression of the DSG1 and DSG2 proteins was significantly lower in EHCC tumour tissues than in normal biliary tract tissues, biliary tract adenoma, and peritumoral tissues (P < 0.05). Adenoma and peritumoral tissues with negative DSG1 and/or DSG2 protein expression exhibited atypical hyperplasia. DSG1 expression was positively correlated with DSG2 expression in EHCC (P < 0.01). In patients with good differentiation, no invasion, no lymph metastasis, TNM I + II stage, and radical surgery, the positive expression of DSG1 and DSG2 proteins was higher (P < 0.05). In comparison to patients with negative DSG1 and/or DSG2 expression, the average overall survival time of those with positive expression was significantly longer (P = 0.000). Cox multivariate analysis revealed that negative DSG1 and DSG2 expressions were independent of poor prognosis factors in EHCC patients. The AUC calculated for DSG1 was 0.681 (95% confidence interval: 0.594-0.768) and that for DSG2 was 0.645 (95% confidence interval: 0.555-0.734), while that for DSG1 and DSG2 was 0.772 (95% confidence interval: 0.609-0.936).

Conclusions: Negative protein expression of DSG1 and DSG2 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviours, and dismal prognosis in EHCC.