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Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas

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Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas

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Título Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas
Autor Gonzaga, Isabela Martins
Lima, Sheila Coelho Soares
Santos, Paulo Thiago de Souza
Blanco, Tania Cristina Moita
Reis, Bruno de Souza Bianchi
Quintella, Danielle Carvalho
Oliveira, Ivanir Martins de
Faria, Paulo Antonio Silvestre de
Kruel, Cleber Dario Pinto
Andreollo, Nelson Adami
Simão, Tatiana de Almeida
Pinto, Luis Felipe Ribeiro
Abstract Background: Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. Methods: We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. Results: Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this signaling pathway is altered in only a small proportion of patients with ESCC. Conclusion: HER receptors target therapies may have the potential to be effective in only a minor fraction of patients with ESCC.
Contido em BMC cancer. London. Vol. 2012 (Dec. 2012), 10p.
Assunto Genes erbB-1
Neoplasias esofágicas
Receptor erbB-2
Terapia de alvo molecular
[en] BRAF
[en] EGFR
[en] Esophageal cancer
[en] HER2
[en] KRAS
[en] Target therapy
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/111812
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