HER2 Ile655Val polymorphism, EGFR expression and cellular proliferation in urinary bladder carcinomas

Abstract

Abstract Background The HER2 gene Ile655Val polymorphism might affect the active conformation of its protein product which would than influence the heterodimerization, signal transduction and the tumor growth. The aim of this work was to investigate the HER2 codon 655 polymorphism and EGFR expression related to proliferative activity of urinary bladder tumors. Methods Eleven urinary bladder carcinomas were analyzed for the presence of HER2 single nucleotide polymorphism at codon 655 using polymerase chain reaction followed by restriction fragment length polymorphism method. Expression of HER2 and EGFR proteins was determined by immunohistochemistry. S-phase fraction and DNA ploidy level were assayed by flow cytometry. Results Co-expression of EGFR and HER2 proteins was detected in 2/8 homozygous cases and in 1/3 heterozygous tumors. The carcinomas positive for EGFR and HER2 receptors from the group with Ile/Val genotype had similar level of S-phase fraction with those from the group with Ile/Ile genotype. The S-phase fraction was higher in heterozygous EGFR positive tumors than in homozygous EGFR positive tumors. The lymph node metastases were present predominantly in cases with Ile/Val genotype than in patients with Ile/Ile genotype. Conclusions Our results suggest that the urinary bladder carcinomas expressing Val allele had a high growth rate and developed an aggressive behavior. These molecular alterations may serve as potential targets for an individualized treatment in urinary bladder cancer. Legal entity responsible for the study Mirela Dumitru. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.