BACKGROUND: Nuclear/cytoplasmic accumulation of beta-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of beta-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of beta-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of beta-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of beta-catenin with the clinical outcome. METHODS: Mutations of the beta-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of beta-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. RESULTS: Nuclear/cytoplasmic accumulation of beta-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the beta-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed beta-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of beta-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no beta-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with beta-catenin accumulation (p = .003). CONCLUSIONS: These findings suggest that beta-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.
BACKGROUND: Nuclear/cytoplasmic accumulation of beta-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of beta-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of beta-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of beta-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of beta-catenin with the clinical outcome. METHODS: Mutations of the beta-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of beta-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. RESULTS: Nuclear/cytoplasmic accumulation of beta-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the beta-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed beta-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of beta-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no beta-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with beta-catenin accumulation (p = .003). CONCLUSIONS: These findings suggest that beta-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.
Authors: William B Laskin; Jerzy P Lasota; John F Fetsch; Anna Felisiak-Golabek; Zeng-Feng Wang; Markku Miettinen Journal: Am J Surg Pathol Date: 2015-02 Impact factor: 6.394
Authors: Riccardo Di Fiore; Rosa Drago-Ferrante; Francesca Pentimalli; Domenico Di Marzo; Iris Maria Forte; Antonella D'Anneo; Daniela Carlisi; Anna De Blasio; Michela Giuliano; Giovanni Tesoriere; Antonio Giordano; Renza Vento Journal: Int J Oncol Date: 2014-08-22 Impact factor: 5.650