BMC Cancer (Dec 2012)

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

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

DOI
https://doi.org/10.1186/1471-2407-12-569
Journal volume & issue
Vol. 12, no. 1
p. 569

Abstract

Read online

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 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.

Keywords