Expression and Mutation Pattern of β-Catenin and Adenomatous Polyposis Coli in Colorectal Cancer Patients

Background and Anns. beta-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of beta-catenin and APC in tumors and lymph nodes in colorectal cancer (CRC) patients and the mutational spectrum of the genes coding these proteins. Methods. Expression of APC and beta-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNBI and the mutation cluster region (MCR) in exon 15 of the APC gene were screened for mutation by PCR-sequencing. Results. Nuclear/cytoplasmic immunostaining of beta-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of beta-catenin correlated with tumor size and with those in lymph nodes. Membranous beta-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous beta-catenin correlated with high invasiveness and metastatic potential. Positive immunostaining for APC was observed in 2 and 14% of tumors and lymph nodes, respectively. Overexpression in nucleus/cytoplasm and lack of membranous beta-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the beta-catenin in the nucleus/cytoplasm. Mutations were identified in the APC gene in 13 tumors and six mutations were novel. Conclusions. Positive association between aberrant expression of beta-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of beta-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor. (C) 2015 IMSS. Published by Elsevier Inc.