Eiji Higaki1,2,3, Takeshi Kuwata1,4, Akiko Kawano Nagatsuma1, Yasunori Nishida1,2, Takahiro Kinoshita2, Masaki Aizawa5, Hiroaki Nitta6, Masato Nagino3, Atsushi Ochiai7,8. 1. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Department of Gastric Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 3. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. 4. Department of Pathology and Clinical Laboratory, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 5. Department of Digestive Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, 951-8566, Japan. 6. Technology and Applied Research, Ventana Medical Systems, Inc., 1910 E Innovation Park Drive, Tucson, AZ, 85755, USA. 7. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. aochiai@east.ncc.go.jp. 8. Department of Pathology and Clinical Laboratory, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. aochiai@east.ncc.go.jp.
Abstract
BACKGROUND: EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. METHODS: 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. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. RESULTS: EGFR GCN gain (≥ 2.5 EGFR signals per cell) was detected in 194 patients (22.7%) and indicated poor prognosis. 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. 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. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. CONCLUSIONS: EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.
BACKGROUND:EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. METHODS: 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. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. RESULTS:EGFR GCN gain (≥ 2.5 EGFR signals per cell) was detected in 194 patients (22.7%) and indicated poor prognosis. 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. 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. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. CONCLUSIONS:EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.
Entities:
Keywords:
Amplification; Dual in situ hybridization; EGFR; Gastric cancer; Gene copy number
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