·57· Journal of International Translational Medicine, June 2018, Vol.6, No.2 ·Original Article · Infuence of HER2 Overexpression on Response to Cetuximab in Patients with Metastatic Colorectal Cancer, Tehran, Iran Rambod MOZAFARI 1 , Amir Hossein EMAMI 1 , Sayyed Reza Safaee NODEHI 1 , Farhad SHAHI 1 , Jayran ZEBARDAST 2 , SeyedAhmad SEYEDALINAGHI 3 , Ali ASADOLLAHI-AMIN 3 1 Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Center, Cancer institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran; 2 Deputy of Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran; 3 Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran Corresponding author: Ali ASADOLLAHI-AMIN, E-mail: amiyaneh@gmail. com Abstract Objective: Colorectal cancer (CRC) remains the fourth cause of mortality in the world. HER2, an epidermal growth factor receptor (EGFR) has an infuence on prognosis and overall survival in breast and metastatic gastric cancers. We evaluated the prevalence of HER2 positivity among Iranian patients with CRC and determined the response rate to Cetuximab, an EGFR- targeted drug in eligible HER2 positive patients. Methods: HER2 immunohistochemistry staining was carried out in samples of 150 CRC patients and the prevalence of HER2 overexpression was estimated. We also investigated the association of HER2 overexpression with the prognostic factors, overall survival (OS), and progression-free survival (PFS) as well as response to Cetuximab in the patients by reviewing the medical records. Results: Te prevalence of HER2 overexpression was12%. Te mean of follow-ups was 40.67 ± 21.57 weeks in the patients with HER2 overexpression. PFS and OS were lower in HER2 overexpressed patient than other. Tere was only a borderline relation between the distant metastasis and HER2 expression. Considering the response to Cetuximab, there was a signifcant diference between HER2 positive and HER2 negative groups. Conclusions: Our study provides further evidence in the efect of HER2 overexpression in CRC patients on the OS, PFS, and response to Cetuximab. Key words Cetuximab; Colorectal cancer; HER2; Overall survival; Prevalence doi: 10.11910/2227-6394.2018.06.02.02 Introduction Colorectal cancer (CRC) is the third leading cause of cancer and the fourth cause of mortality in the world [1,2] . In Iran, a four year period of age-standardized rates of CRC has been reported 38/100,000 with significantly higher proportion in men than women. Regarding high risk lifestyle for CRC, smoking, alcohol consumption and drug abuse is more common in Iranian men whereas, inactivity is often seen in women. In addition, genetic factors may play a more important role in the nature of CRC than the others [3] . Nowadays, monoclonal antibodies against members of the epidermal growth factor receptor (EGFR) are widely using in metastatic colorectal cancer (mCRC) patients with promising results [4] . Cetuximab is the Food and Drug Administration (FDA) approved monoclonal antibody for patients with EGFR-expressing mCRC. According to in vitro, in vivo and clinical trial studies of Cetuximab; it has shown a dramatic cell cycle arrest through EGFR-cell signal transduction, as well as activation of pro-apoptotic proteins like Bax [5, 6] . Intracellular signal activation and transduction of EGFR is performed by KRS protein [7] . Approximately 35%-45% of colorectal tumors are known to have a mutated (abnormal) KRAS gene [8,9] . National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO) and European Medicines Evaluation Agency recommended testing for KRS gene mutations in advanced CRC patients. KRS testing was added to 2009 clinical practice guidelines