Affiliations: [a] Fudan University Shanghai Cancer Center, Department of Colorectal Cancer and Oncology, Shanghai Medical College Fudan University, Shanghai, China | [b] Department of Human Anatomy and Histo-Embryology, Shanghai Medical College of Fudan University, Shanghai, China
Correspondence:
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Corresponding author: Dr. Sanjun Cai, Department of Colorecal Surgery, Fudan University Shanghai Cancer Hospital, 270 Dongan Road, Shanghai 200032, China. Tel.: +86 21 64175590; Fax: +86 21 64035387; E-mail: bobojpn@hotmail.com.
Abstract: Background:As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) have become efficacious drug targets in this setting. But until now, although above studies suggested that EGFR and Her2 may serve as effective biomarkers for targeted therapy in cancer patients with primary tumor, the information on these biomarkers in colorectal cancer is still limited in metastases. Objective:The purpose of this study is to evaluate the expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) on the lymph node metastasis (LNM) of colorectal cancer (CRC), develop LNM-associated biomarkers for CRC. Methods:Differences in EGFR and Her2 expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in a total of 126 Chinese colorectal carcinoma samples using quantitative real-time PCR analysis and western blot. Confirmation assay with immunohistochemistry (IHC) study was applied in the same samples. The relationship to clinicopathological parameters and prognosis of candidate biomarkers was also examined in the same samples. Results:EGFR and Her2 were significantly upregulated in LNM CRC compared to non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction, western blot. Similar results were confirmed in the immunohistochemistry (IHC) assay. Overexpression of EGFR and Her2 were significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that EGFR and Her2 expression were useful independent prognostic factor for recurrence and survival of CRC patients (P < 0.05). Conclusions:EGFR and Her2 might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of EGFR or Her2 is a potential predict factor to the poor outcome in clinical colorectal cancer.
