title: High EGFR and low p-Akt expression is associated with better outcome after nimotuzumab-containing treatment in esophageal cancer patients: preliminary clinical result and testable hypothesis.
abstract: The epidermal growth factor receptor (EGFR) is widely overexpressed in esophageal squamous cell carcinoma (ESCC) and it results is associated with a poor prognosis. Identifying the subgroup of ESCC patients who are sensitive to EGFR-targeted therapy is a key point to facilitate its medical use.We retrospectively analyzed 32 ESCC patients treated with the combination of nimotuzumab (h-R3) and radiotherapy (RT) or chemoradiotherapy (CRT). Expression of EGFR and phosphorylated proteins associated with EGFR signaling pathway, i.e. p-Akt and p-Erk, were assessed with immunohistochemistry (IHC) for all patients. Correlations between these proteins' expression levels and overall survival (OS) were assessed.High expression of EGFR, p-Akt and p-Erk was detected in 53.1% (17/32), 54.8% (17/31) and 59.4% (19/32) of tumors respectively. No significant differences in OS were found between high EGFR, p-Akt and p-Erk expression groups and their respective counterparts. Of note, significantly better overall survival was observed in patients with coexistence of high EGFR expression and low p-Akt expression (p = 0.030).Our data allowed us to put forward a hypothesis that high EGFR and low p-Akt expression may predict a clinical benefit of EGFR antagonists such as nimotuzumab combined with RT or CRT. This can be discussed in the terms of oncogene addiction and synthetic lethality concepts. This hypothesis can be further tested in larger groups of patients.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jia-ying
authors.initials: JY
authors.lastname: Deng
authors.affiliation: Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xu-wei
authors.initials: XW
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiao-long
authors.initials: XL
authors.lastname: Fu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xi-chun
authors.initials: XC
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Jia-qing
authors.initials: JQ
authors.lastname: Xiang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Ya-wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Hai-quan
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Center of Molecular Immunology, Havana, Cuba.
authors.forename: Rolando
authors.initials: R
authors.lastname: Perez
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Guo-liang
authors.initials: GL
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Kuai-le
authors.initials: KL
authors.lastname: Zhao
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000628:therapy*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C501466:nimotuzumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: EGFR; esophageal squamous cell carcinoma; monoclonal antibody; p-Akt; p-Erk