Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer

Abstract

Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad prognosis. Specific therapies are now developed against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study was aimed at assessing their expression in a large series of SCCO, as well as their potential therapeutic interest in this pathology. Immunohistochemical expression of these factors was assessed retrospectively in 107 cases of SCCO with primary surgery, as well as their relationships to recurrence, metastasis and overall survival on a long-term follow-up. Human epidermal growth factor receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases, and VEGF in 38.3%. Epidermal growth factor receptor overexpression was significantly related to vascular invasion (P ¼ 0.023). Its diffuse positivity was significantly related in multivariate analysis to higher local recurrence (P ¼ 0.006) and lower overall survival (P ¼ 0.003), in a subgroup of patients of poor outcome who had received postoperative adjuvant treatment. These results highlight the great potential prognostic and therapeutic interest of evaluating EGFR diffuse positivity in locally advanced SCCO.

Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas

“…In patients with head and neck, ovarian, cervical, bladder, and esophageal squamous cell carcinomas, EGFR expression is a strong prognostic indicator that correlates with both higher recurrence rates and shorter survival. [11][12][13]17,21,22,[25][26][27][35][36][37][38] In the current study, we demonstrated that EGFR expression in esophageal adenocarcinoma correlates with outcome in patients who are treated with esophagectomy alone. Our data showed that EGFR expression is correlated strongly with poor overall and disease-free survival in univariate analyses with a trend toward correlation in multivariate analyses.…”

“…Patients who had tumors that expressed EGFR had shorter disease-free and overall survival compared with patients who had EGFR-negative tumors, but EGFR expression was not an independent prognostic indicator for either parameter in multivariate analysis. Although there have been several studies of EGFR expression in esophageal squamous cell carcinomas, 21,[25][26][27][35][36][37][38] studies of the role of EGFR in esophageal adenocarcinomas have been limited. 28,29,39 Similar to our studies, the majority of the esophageal adenocarcinomas in previous studies were from the lower one-third of the esophagus or from the GEJ.…”

“…In turn, this homodimerization or heterodimerization stimulates phosphorylation of the intracellular tyrosine kinases on the receptor, leading to the activation of various downstream signal-transduction pathways that ultimately regulate cell proliferation, migration, adhesion, differentiation, and survival. 10 Protein overexpression or gene amplification of EGFR has been reported in several human tumors of epithelial origin, including head and neck, [11][12][13] thyroid, 14 breast, 15,16 ovarian, 17 , colon, [18][19][20][21] cervix, bladder, 22 stomach, and lung 23 cancers. In a subset of these tumors, most notably breast cancer, 16,19,24 colorectal cancer, [18][19][20][21] and esophageal squamous cell carcinoma, 21,25,26 increased EGFR expression has been associated with advanced disease, development of metastases, and poor clinical prognosis.…”

Characterization of the expression and clinical features of epidermal growth factor receptor and vascular endothelial growth factor receptor-2 in esophageal carcinoma

“…The abnormal activation of EGFR promotes tumorigenesis and proliferation through regulating cell signaling transduction, cell proliferation, apoptosis and angiogenesis. Gibault et al (15) demonstrated that EGFR overexpression was significantly correlated with vascular invasion (P=0.023), local recurrence (P=0.006) and a lower survival rate (P=0.003). In addition, a further study found that EGFR inhibitors were able to inhibit the overexpression of EGFR and human epidermal growth factor receptor-2, thereby inhibiting the proliferation of esophageal cancer cell lines (16).…”

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of esophageal carcinoma and the suggested mechanisms of action

“…Increased EGFR expression may influence multiple aspects of tumor biology, including survival, proliferation of cells, motility, invasiveness and resistance to treatment (8)(9)(10). The success of active small molecule tyrosine kinase inhibitors (TKIs) targeted against EGFR in treating non-small cell lung cancer (NSCLC) has prompted research into their clinical benefits in numerous other solid tumors.…”