title: Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of VIP Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Medical Oncology, Chifeng City People's Hospital, Chengfeng, Inner Mongolia, China.
authors.forename: Changwu
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Henan Province, Zhengzhou, Henan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Shaoxuan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
authors.affiliation: Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D043844:Crown Ethers / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D043844:Crown Ethers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011799:Quinazolines; C531470:icotinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; amplification; esophageal cancer; icotinib; overexpression