Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

Xi Wang,Haitao Niu,Yun Ling,Jing Huang,Weiwei Li,Lei Guo,Changwu Ma,Ying Liu,Wei Liu,Ping Lu,Qingxia Fan,Jianming Ying,Shaoxuan Hu

doi:10.18632/oncotarget.8271

Abstract

This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

Highlights

Esophageal cancer is the sixth most common cause of cancer death all over the world [1]
The prevalence of epidermal growth factor receptor (EGFR) expression in esophageal squamous cell carcinoma (ESCC) patients has rendered it an appealing candidate for targeted therapy, yet whether the overexpression or gene amplification of EGFR could predict the response to EGFR TKI therapy in ESCC patients remains unclear
Our study reported the response rate was 17.6% for ESCC patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors

Summary

Introduction

Esophageal cancer is the sixth most common cause of cancer death all over the world [1]. Most patients in China present with an advanced or metastatic stage and the dominating type is esophageal squamous cell carcinoma (ESCC). Cytotoxic chemotherapy (cisplatin combined with fluorouracil or paclitaxel) remains the main stay of treatments for patients with metastatic ESCC [3,4,5], despite the fact that targeted therapy has already played an important role in other cancer types such as non-smallcell lung cancer, breast cancer, colon cancer and gastric cancer etc. EGFR gene is involved in a wide variety of malignancies such as non-small cell lung cancer, colon cancer and head-and-neck squamous cell carcinoma [7]. EGFR expression was usually associated with more advanced tumor stage as well as reduced overall survival for patients with esophageal and esophagogastric junction adenocarcinomas [8].

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