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 |
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Rok vydání: | 2014 |
Předmět: |
Adult
Male Pathology medicine.medical_specialty Cytoplasm Adenomatous polyposis coli Colorectal cancer Adenomatous Polyposis Coli Protein Exon medicine Humans Neoplasm Invasiveness Wnt Signaling Pathway beta Catenin Aged Aged 80 and over Cell Nucleus biology Wnt signaling pathway General Medicine Exons Middle Aged medicine.disease Catenin Mutation biology.protein Cancer research Immunohistochemistry Female Lymph Lymph Nodes Colorectal Neoplasms Immunostaining |
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 |
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