Immunohistochemical Analyses of Colon Cancer in I1307K APC Mutation Carriers Compared with Noncarriers

Abstract

The I1307K APC germline mutation is associated with an increased risk to colorectal cancer (CRC). Whether and to what extent the somatic features and the molecular pathways of cancer development in mutation carriers differ from colorectal cancer in noncarriers remains unknown. To gain insight into this issue, 52 Israeli patients with CRC, 24 of whom were I1307K APC mutation carriers, were analyzed. The expression pattern of genes known to be involved in the pathogenesis of sporadic CRC was assessed immunohistochemically: E-cadherin, ß-catenin, deleted in colon cancer (DCC), and p53. In addition, tumors were genotyped for somatic activating mutations in Ki-rasoncogene. Mutation carriers and noncarriers were comparable in age at diagnosis (64.3 ± 10.1 years for carriers and 60.8 ± 14.1 years for noncarriers), tumor location in the colon, and disease stages. Tumors of I1307K mutation carriers displayed positive p53 immunostaining and loss of ß-catenin, E-cadherin, and DCC expression more often compared with noncarriers, although none of these differences reached statistical significance. Mutation frequencies in the Ki-ras gene were similar in both groups. In conclusion, the molecular pathways in CRC in I1307K APC mutation carriers are seemingly similar to those of sporadic cases, but a larger study is clearly needed.