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

Abstract

Abstract. Alterations of the epidermal growth factor receptor (EGFR), including overexpression or gene mutations, contribute to the malignant transformation of human epithelial cells. The aim of this study was to assess EGFR overexpression or gene amplification in esophageal squamous cell carcinoma (ESCC) tissue samples and investigate their correlations with biological behaviors. Tissue specimens from 56 patients with surgically resected ESCC were obtained for immunohistochemical analysis of EGFR expression and fluorescence in situ hybridization analysis of EGFR amplification. The data were statistically analyzed to determine the associations with patient clinicopathological and survival data. EGFR was overexpressed in 30 of the 56 (53.6%) ESCC samples and was associated with poor tumor differentiation (P=0.047). EGFR amplification was detected in 13 cases (23.2%) and was associated with advanced pathological stage (P=0.042) and tumor lymph node metastasis (P=0.002). The univariate analysis identified no association between EGFR overexpression and the overall survival (OS) of the patients. By contrast, EGFR amplification predicted ESCC prognosis (P= 0.031), while the multivariate analysis revealed a marginal statistical significance for the association between EGFR amplification and OS (P=0.056). EGFR overexpression and increased EGFR copy number were common events in ESCC and contributed to malignant biological behaviors, including tumor dedifferentiation and lymph node metastasis. EGFR amplification may therefore be useful in predicting OS in patients with ESCC. IntroductionEsophageal cancer represents the sixth most frequent cause of cancer-related mortality worldwide (1). Histologically, esophageal cancer is classified primarily as either squamous cell carcinoma (SCC) or adenocarcinoma. Esophageal SCC (ESCC) accounts for approximately one-third of esophageal cancer cases in the United States and >90% of esophageal cancer cases worldwide (2,3). The risk factors for ESCC include tobacco smoking, heavy alcohol consumption and a diet lacking fresh fruits and vegetables (2,3). To date, the prognosis of esophageal SCC remains poor, despite improvements in surgical techniques, perioperative management, chemotherapy and/or radiotherapy (4-6). Thus, studies on early detection, novel treatment options, prevention and predictive tumor markers for ESCC treatment and prognosis are urgently required.Epidermal growth factor receptor (EGFR) is a part of an important transmembrane signal transduction pathway in human epithelial cells and altered EGFR protein expression or gene amplification occurs in a number of solid tumors, including esophageal cancer (7-13). EGFR-mediated signaling is crucial for cell proliferation, as well as for cancer progression, including tumor angiogenesis, metastasis and cancer cell resistance to apoptosis. 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...

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

“…In addition, the expression of NCOA5 in normal tissues was higher compared with that in tumor tissues. As the level of tumor differentiation and TNM stage are important indicators of the malignant degree of tumors, the results of the present study suggest that the decreased expression of NCOA5 may be involved in the promotion of tumor progression (28)(29)(30).…”

Amplification and overexpression of CTTN and CCND1 at chromosome 11q13 in Esophagus squamous cell carcinoma (ESCC) of North Eastern Chinese Population

“…Amplification and overexpression of EGFR has been reported in ESCC and was significantly associated with a poor prognosis in ESCC patients indicating that it may play an important role in ESCC progression 29,30…”

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

“…IKKα reduction has been reported in human skin, lung, oral, esophageal, nasopharyngeal, and head and neck SCCs (Liu et al, 2006; Maeda et al, 2007; Marinari et al, 2008; Xia et al, 2013; Yan et al, 2014). HESCCs frequently acquire increased EGFR activity and decreased p53, p16, and Rb expression (Lin et al, 2015; Stoner and Gupta, 2001). However, the role of IKKα in ESCC has not been explored.…”