Expression of CDX2 and hepatocyte antigen in benign and malignant lesions of gallbladder and its correlation with histopathologic type and clinical outcome

Abstract

Recent studies have shown that both CDX2 and Hepatocyte antigen (Hep) are detected in different types of cancer and associated with clinical prognosis. However, fever studies have examined gallbladder cancer specimens, and little is known about the clinicopathological significance of both CDX2 and Hep expression in gallbladder adenocarcinomas. In present study, we examined the expression frequencies of CDX2 and Hepatocyte antigen (Hep), and explored their clinicopathologic significances in gallbladder adenocarcinoma. Immunohistochemistry was used to detect and compare the frequencies of CDX2 and Hep expression in 108 samples of gallbladder adenocarcinoma, 46 peri-tumor tissues and 35 chronic cholecystitis. The expression frequencies for CDX2 and Hep were 49/108 (45.4%) and 45/108 (41.7%) in gallbladder carcinoma; 13/46 (28.3%) and 11/46 (23.9) in peri-tumor tissues; 5/35 (14.3%) and 2/35 (5.7%) in chronic cholecystitis. The positive staining of CDX2 or Hep in gallbladder adenocarcinoma was significantly higher than that in peritumoral tissues (both, P < 0.05), and chronic cholecystits (both, P < 0.01). The expression of CDX2 or Hep was negatively correlated to grade of differentiation, tumor size and lymph node metastasis (P < 0.01 or P < 0.05). Elevated expression frequency of CDX2 or Hep was associated with increased overall survival (P = 0.003 or P = 0.002). Multivariate Cox regression analysis showed that CDX2 (P = 0.014) or Hep (P = 0.026) expression was an independent prognostic predictor in gallbladder adenocarcinoma. CDX2 and Hep might function as important biological markers in the development and prognosis of gallbladder adenocarcinoma.

Fig. 1

Immunohistochemical staining of CDX2 in gallbladder adenocarcinoma and peritumoral tissue (×200). a CDX2 positive staining was observed in nuclei of a representative moderately-differentiated gallbladder adenocarcinoma. b CDX2 expression was located in nuclei of a representative peritumoral tissue with severely-atypical hyperplasia

Fig. 2

Expression of Hep in gallbladder adenocarcinoma and chronic cholecystitis (×200). a Positive staining of Hep was seen in cytoplasms in a representative well-differentiated adenocarcinoma. b Positive expression of Hep was detected in cytoplasms of a representative chronic cholecystitis with moderately-atypical hyperplasia. c Typical Hep staining of hepatocytes in a liver section

Fig. 3

Kaplan-Meier plots for overall survival in 67 patients with gallbladder adenocarcinoma surgery in relation to CDX2 and Hep expression. a Positive or increased CDX2 expression was associated with increased over survival (P = 0.003, log rank test). b Hep expression was also related to increased overall survival (P = 0.02, log rank test)