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

// Chun-yu Wang 1,* , Jia-ying Deng 1,* , Xu-wei Cai 2 , Xiao-long Fu 2 , Yuan Li 3 , Xiao-yan Zhou 3 , Xiang-hua Wu 4 , Xi-chun Hu 4 , Min Fan 1 , Jia-qing Xiang 5 , Ya-wei Zhang 5 , Hai-quan Chen 5 , Rolando Perez 6 , Guo-liang Jiang 1 and Kuai-le Zhao 1 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 3 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China 5 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 6 Center of Molecular Immunology, Havana, Cuba * These authors share first authorship Correspondence to: Kuai-le Zhao, email: // Guo-liang Jiang, email: // Keywords : esophageal squamous cell carcinoma, EGFR, p-Akt, p-Erk, monoclonal antibody Received : April 13, 2015 Accepted : May 31, 2015 Published : June 08, 2015 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.