Expression and mutation pattern of β-catenin and adenomatous polyposis coli in colorectal cancer patients

Autor: Lobna Ayadi, Rania Abdelmaksoud-Damak, Mounir Frikha, Imen Miladi-Abdennadher, Slim Charfi, Mouna Triki, Abdelmajid Khabir, Tahia Sellami-Boudawara, Raja Mokdad-Gargouri
Rok vydání: 2014
Předmět:
Zdroj: Archives of medical research. 46(1)
ISSN: 1873-5487
Popis: Background and Aims β-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of β-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 β-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNB1 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 β-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of β-catenin correlated with tumor size and with those in lymph nodes. Membranous β-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous β-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 β-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the β-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 β-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of β-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor.
Databáze: OpenAIRE