Anaphase-Promoting Complex 7 is a Prognostic Factor in Human Colorectal Cancer

ABSTRACT

PURPOSE: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity and is required for ubiquitination of securin and cyclin-B. Several APC-targeting molecules are reported to be oncogenes. Dysregulation of APC may be associated with tumorigenesis. This study examines the relationship between APC expression and clinicopathological factors and evaluates the possibility of an aberrant APC function in colorectal carcinomas (CRCs). METHODS: To determine whether the loss of APC7 expression is related to tumorigenesis, we used tissue micro-arrays in 114 resected CRCs to scrutinize the expressions of APC7 and Ki-67 immunohistochemistry and to find relations with clinocopathologic parameters. The expression of APC7 was defined as positive for summed scores of staining intensities from 0 to 3+. RESULTS: Forty-four cases (67.7%) of colon cancer and 38 cases (77.6%) of rectal cancer showed immunopositive reactions to APC. The grade of APC expression was not statistically correlated with tumor location, age, T or TNM stage, or differentiation. However, the expression of APC did correlate with the expression of Ki-67 and to the tumor recurrent. Higher APC expression showed the better 5-year overall survival rate in 74% of grades 2, 3 groups (high expression) than 57% of grades 0, 1 groups (lower expression) respectively (P = 0.042). CONCLUSION: Positive APC expression may be a good prognostic factor for patients with CRC, and the loss of APC expression in tumor tissue may be related with the risk for recurrence and a poor survival rate compared to high APC expression. Further study of APC in controlling the cell cycle as aberrant function in CRC is needed.