Immunohistochemical Expression and Prognostic Value of CD97 and Its Ligand CD55 in Primary Gallbladder Carcinoma

BACKGROUND CD97 as a member of the EGF-TM7 family with adhesive properties plays an important role in tumor aggressiveness by binding its cellular ligand CD55, which is a complement regulatory protein expressed by cells to protect them from bystander complement attack. Previous studies have shown that CD97 and CD55 both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. The aim of this study was to investigate CD97 and CD55 expression in primary gallbladder carcinoma (GBC) and their prognostic significance. METHODS Immunohistochemistry was used to investigate the expression of CD97 and CD55 proteins in 138 patients with GBC. RESULTS CD97 and CD55 were absent or only weakly expressed in the normal epithelium of the gallbladder but in 69.6% (96/138) and 65.2% (90/138) of GBC, respectively, remarkably at the invasive front of the tumors. In addition, CD97 and CD55 expressions were both significantly associated with high histologic grade (both P = 0.009), advanced pathologic T stage (P = 0.01 and 0.009, resp.) and clinical stage (both P = 0.009), and positive venous/lymphatic invasion (both P = 0.009). Multivariate analyses showed that CD97 (hazard ratio, 3.236; P = 0.02) and CD55 (hazard ratio, 3.209; P = 0.02) expressions and clinical stage (hazard ratio, 3.918; P = 0.01) were independent risk factor for overall survival. CONCLUSION Our results provide convincing evidence for the first time that the expressions of CD97 and CD55 are both upregulated in human GBC. The expression levels of CD97 and CD55 in GBC were associated with the severity of the tumor. Furthermore, CD97 and CD55 expressions were independent poor prognostic factors for overall survival in patients with GBC.