ABSTRACT
Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10×10-9 and P=6.74×10-8, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ~2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43-2.10; P=2.37×10-8 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80×10-10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival.
ABSTRACT
OBJECTIVES: To investigate the clinical and prognostic significance of high vascular endothelial growth factor (VEGF) expression in resected T3 gastric adenocarcinoma (GA). METHODS: Data of VEGF expression on 453 patients with resected T3 GA were collected from a single institute in Fuzhou, China. VEGF expression in the resected tumor tissues was evaluated by immunohistochemistry (IHC). Associations between VEGF expression outcomes and prognosis were investigated using by the χ(2) test, Kaplan-Meier plus log-rank test, and univariate and multivariate Cox models. RESULTS: In total, 48.6% (220/453) patients had low VEGF expression (IHC score ≤2+). Patients with high VEGF expression (IHC>2+; 233/453, 51.4%) had significantly poorer median recurrence-free survival time (20 vs 55 months, P < 001) and median overall survival time (28 vs 58 months; P < 001) than patients with low VEGF. High VEGF was associated with higher overall recurrence (68.2% vs 51.4%, P = 2.675 × 10(-4)), poorer overall survival (27.5% vs 47.3%, P = 1.719 × 10(-5)), and increased risk of recurrence (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.33-2.19; P = 2.43 × 10(-5)) and death (HR, 1.80; 95% CI, 1.41-2.3; P = 2.19 × 10(-6)). CONCLUSIONS: High VEGF expression is associated with a higher risk of recurrence and shorter survival in resected T3 GA. These findings may provide a foundation for evaluating VEGF-targeted molecular therapies in T3 GA.
Subject(s)
Adenocarcinoma/metabolism , Neoplasm Recurrence, Local/metabolism , Stomach Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Biomarkers, Tumor/metabolism , Disease-Free Survival , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Antigen KI-67 (Ki67) plays a critical role in regulation of cell proliferation and has prognostic value in several types of cancer; however, the relationship between Ki67 expression and prognosis in resected T3 gastric adenocarcinoma (GA) has not yet been investigated. METHODS: Retrospective analysis of 693 patients with T3 GA who underwent surgical resection at a single institution between July 2003 and December 2009 was performed. Ki67 expression in tumor tissues was examined using immunohistochemistry (IHC); the associations between Ki67 and prognosis/survival outcomes were assessed using the Chi-square test, Kaplan-Meier survival analysis, log-rank test, and univariate and multivariate analysis. RESULTS: High Ki67 expression (IHC score > or = 3+) was observed in 335/693 (48.34%) of cases. Ki67 expression was significantly associated with distant metastasis, 5-year median recurrence-free survival time in months (MRFST), and 5-year median overall survival time in months (MOST). Median recurrence and overall survival were 20 and 28 months. High Ki67 expression was associated with shorter MRFST (13 vs. 27 months, p < 0.001) and MOST (21 vs. 35 months, p < 0.001 compared to low K67 expression). Multivariate analysis demonstrated that high K167 expression was an independent prognostic factor for an increased risk of recurrence (p = 0.001) and distant metastasis (p = 0.003) and poorer overall survival (p = 5.33 x 10(-5)). CONCLUSIONS: High Ki67 expression was frequently observed in resected T3 GA and was a significant prognostic factor for poor outcome with respect to recurrence, distant metastasis and overall survival. Ki67 may represent a useful prognostic biomarker for resected T3 GA.
