Impact of Insulin-Like Growth Factor Type 1 Receptor, Epidermal Growth Factor Receptor, and HER2 Expressions on Outcomes of Patients with Gastric Cancer

• Published in: Clinical cancer research Vol. 14; no. 10; pp. 3022 - 3029
• Main Authors: Matsubara, Junichi, Yamada, Yasuhide, Hirashima, Yoshinori, Takahari, Daisuke, Okita, Natsuko T, Kato, Ken, Hamaguchi, Tetsuya, Shirao, Kuniaki, Shimada, Yasuhiro, Shimoda, Tadakazu
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 15.05.2008
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - analysis; EGFR; Female; gastric cancer; Gene Expression; HER2; Humans; IGF-IR; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; prognostic factor; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, ErbB-2 - biosynthesis; Receptor, IGF Type 1 - biosynthesis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-1898

Purpose: Expression levels of insulin-like growth factor type 1 receptor (IGF-IR), epidermal growth factor receptor (EGFR), and HER2 expressions have been linked to clinical outcomes in several solid tumors. However, the clinical significance of these biomarkers in gastric cancer (GC) remains unclear. This study was designed to delineate the clinical implications of these three biomarkers in GC. Experimental Design: The study group comprised 87 patients who underwent gastrectomy at National Cancer Center Hospital and subsequently received chemotherapy for recurrent or residual tumors. Using immunohistochemical techniques, we analyzed the expressions of IGF-IR, EGFR, and HER2 on formalin-fixed paraffin-embedded specimens of surgically removed primary tumors. Results: IGF-IR expression (defined as >10% membranous staining) was found in 67 tumors (77%), EGFR expression in 55 (63%), and HER2 expression in 16 (18%). Positive coexpression of IGF-IR and EGFR was found in 48 tumors (55%), that of IGF-IR and HER2 in 16 (18%), and that of EGFR and HER2 in 13 (15%). Multivariate survival analysis showed that IGF-IR–positive expression [hazard ratio (HR) 2.14, 95% confidence interval (95% CI) 1.20-3.82; P = 0.01], performance status 1 or 2 (HR 1.83, 95% CI 1.15-2.91; P = 0.01), and diffuse type tumors (HR 1.71; 95% CI 1.08-2.70; P = 0.02) were significant predictors of poor survival. Conclusions: IGF-IR expression in surgical GC specimens, poor performance status, and diffuse type tumors are significant predictors of poor outcomes in patients with GC. Our data suggest that anti–IGF-IR strategies may prove valuable in such patients.