Inhibitors of EGFR activity include specific monoclonal antibodies and small molecule tyrosine kinase inhibitors that are used for standard therapy of lung and colorectal as well as head and neck cancers. EGFR GCN alterations occur in a wide range of cancers and serve as a marker of poor prognosis. detected amplification of genes encoding RTKs, including KRAS, HER2, EGFR, MET, and FGFR2, in approximately 37 % of gastric cancers, and suggested that amplification of these genes may act as an oncogenic driver often related to poor prognosis.ĮGFR resides on chromosome 7p12 and encodes a 170-kDa RTK that contributes to cancer progression by mediating cellular proliferation, migration, invasion, and metastasis. The results of other studies suggest the potential efficacy of targeted therapy against gene alterations in gastric cancers, and several other therapeutic drugs against these RTKs, including EGFR, are currently under investigation. The results of a recent ToGA trial revealed that the anti-HER2 antibody trastuzumab improves the survival of patients with HER2-positive advanced gastric cancer. In contrast, evidence indicates that amplification, overexpression, or epigenetic deregulation may have an important role in tumor progression. In gastric cancer, mutations in genes encoding components of the receptor tyrosine kinase (RTK)/RAS-signaling pathway are infrequent. Thus, there is an urgent need for the development of more effective drugs, particularly those targeting tumor progression mechanisms. Despite recent improvements in surgical approaches combined with chemotherapy and radiotherapy, the benefits of chemotherapy for advanced gastric cancer are still limited. Annually, 989,600 new patients are diagnosed, and 738,000 people die of this disease. Gastric cancer is the second leading cause of cancer-related death worldwide. ConclusionsĮGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN non-gain patients and were distributed between IHC 0/1+ and 2+ subgroups. Among 194 patients, EGFR amplification ( EGFR/CEN7 ≥ 2.0) was observed in 29 patients (14.9 %), which was almost identical to the IHC 3+ subgroup and worst prognostic subgroup. ResultsĮGFR GCN gain (≥2.5 EGFR signals per cell) was detected in 194 patients (22.7 %) and indicated poor prognosis. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer.
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