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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

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

Authors: Isabela Martins Gonzaga, Sheila Coelho Soares-Lima, Paulo Thiago Souza de Santos, Tania Cristina Moita Blanco, Bruno Souza Bianchi de Reis, Danielle Carvalho Quintella, Ivanir Martins de Oliveira, Paulo Antonio Silvestre de Faria, Cleber Dario Pinto Kruel, Nelson Adami Andreollo, Tatiana Almeida de Simão, Luis Felipe Ribeiro Pinto

Published in: BMC Cancer | Issue 1/2012

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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.
Appendix
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Metadata
Title
Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas
Authors
Isabela Martins Gonzaga
Sheila Coelho Soares-Lima
Paulo Thiago Souza de Santos
Tania Cristina Moita Blanco
Bruno Souza Bianchi de Reis
Danielle Carvalho Quintella
Ivanir Martins de Oliveira
Paulo Antonio Silvestre de Faria
Cleber Dario Pinto Kruel
Nelson Adami Andreollo
Tatiana Almeida de Simão
Luis Felipe Ribeiro Pinto
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-569

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