Squamous Cell Carcinoma of the Esophagus: Evaluation of the Status of Epidermal Growth Factor Receptors (EGFR and HER-2) by Immunohistochemistry and in Situ Hybridization

Abstract

We performed a parallel evaluation of the status of epidermal growth factor receptors EGFR and HER-2 in tumor samples from 31 patients with squamous cell carcinoma of the esophagus. Hyperexpression of proteins was detected by immunohistochemical methods and gene amplification and other chromosome abnormalities were studied using FISH reaction. Evaluation of EGFR status showed that amplification of EGFR gene was present in 25% cases and chromosome 7 polysomy was detected in 29.2% cases positive by protein expression (2+/3+). Immunohistochemically positive EGFR status was confirmed by the results of FISH reaction for gene amplification and chromosome 7 polysomy in 54.2% cases (p=0.002). During evaluation of HER-2 status in the tumor, hyperexpression of the protein detected histochemically was not confirmed by FISH reaction for detection of amplification of the corresponding gene in 16.1% cases. In 22.6% patients, chromosome 7 polysomy was detected; it was not accompanied by amplification of HER-2 gene, but was related to immunohistochemically positive status of the tumor. Hyperexpression of EGFR protein significantly correlated with the presence of intravascular invasion (p=0.006) and increased depth of invasion (p=0.044), while amplification of EGFR gene (≥2.2) correlated with low differentiation degree of the tumor (p=0.006). The outcome of the disease was not associated with EGFR status at the gene and protein levels, whereas clinical course of the disease in patients with immunohistochemically negative expression of HER-2 protein was more favorable than in patients with positive expression (p=0.004). The results of this study suggest that hyperexpression/amplification of EGFR and hyperexpression of HER-2 are important clinical markers for evaluation of disease prognosis and development of new regimens of targeted therapy for patients with squamous cells carcinoma of the esophagus.

Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma

“…The present study revealed that EGFR protein expression was associated with ESCC dedifferentiation, whereas EGFR gene amplification was associated with advanced stage and lymph node metastasis. These data are consistent with the results of previous studies (14)(15)(16)(17)(18)(19). Furthermore, Nicholson et al (31) demonstrated that EGFR overexpression is correlated with prognosis in esophageal, head and neck, ovarian, cervical and bladder cancer.…”

“…Previous studies also demonstrated that EGFR overexpression/gene amplification may be indicative of unfavorable parameters for ESCC (16,17). For example, Delektorskaya et al (18) reported that overexpression of the EGFR protein is significantly correlated with tumor intravascular invasion and depth of invasion, whereas EGFR gene amplification is associated with tumor dedifferentiation. Kitagawa et al (19) demonstrated a significant correlation between EGFR gene amplification and ESCC lymph node metastasis.…”

“…EGFR overexpression is mostly due to EGFR gene amplification or mutations, with the latter occurring frequently in EGFR exons 18-21, which encode the tyrosine kinase section of the EGFR protein. Previous studies have demonstrated an association between EGFR alterations and aggressive biological behaviors (e.g., tumor cell dedifferentiation, advanced tumor stage or cancer metastasis) of different human cancers of epithelial origin, including head and neck, breast, colon, stomach and lung cancer (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) (20)(21)(22). EGFR amplification and protein overexpression have been reported in ESCC and premalignant lesions (3,9,19) and the overexpression of EGFR was found to be significantly associated with the depth of invasion of the tumor (9).…”

Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

“…The results may be associated with the lifestyle of the Kazakh ethnic group, such as longterm excessive consumption of smoked meat, fermented foods, alcohol and tobacco, spicy foods, and lack of vegetables and foods rich in vitamins (1,20). In the future, the most sensitive probes should be selected to improve the early diagnosis of EC using molecular pathological techniques (9,10,21).…”

Nano‐sized Carrier Systems as New Materials for Nuclear Medicine

“…Most tumors highly overexpress receptors for such growth factors, which make growth factors highly attractive as targeting moieties. The most commonly studied growth factor receptors hyperexpressed in tumor tissue are vascular endothelial growth factor receptor (VEGFr) [62][63][64][65] and endothelial growth factor receptor (EGFr) [66][67][68]. Recently it was shown on more than 1000 human biopsia samples that receptor for follicle-stimulating hormone (FSHr) [69], in healthy adult expressed only in gonades (testes and ovaria), is largely (in > 90% cases) overexpressed in the vascularization zone of nearly all types of malignant tumors, being another promise for a holy grail of universal tumor targeting approach.…”