Prognostic Impact of Phosphorylated Mitogen-Activated Protein Kinase Expression in Patients with Metastatic Gastric Cancer

Background: This study was designed to investigate the expression of phosphorylated mitogen-activated protein kinase (p-MAPK/Erk1 and Erk2) and its correlation with outcomes in patients with metastatic gastric cancer. Methods: p-MAPK was detected by immunohistochemistry using monoclonal antibodies in a total of 223 formalin-fixed, paraffin-embedded samples obtained from 156 patients who received first-line chemotherapy in a phase III trial. Results: p-MAPK was positive in 93 (59.6%) and negative in 63 (40.4%) of the 156 patients evaluated. Similar rates of p-MAPK positivity were found in primaries (53%) and metastatic lesions (61.4%). Overall survival was significantly shorter in p-MAPK-positive patients (13.7 vs. 8.5 months) in the univariate analysis. However, this prognostic value disappeared as a trend in the multivariate analysis (p = 0.1). There was a strong, positive correlation between p-MAPK and the MIB-1 proliferation index, but MIB-1 did not predict outcomes. Conclusion: p-MAPK expression could be a potential negative prognostic parameter in patients with metastatic gastric cancer treated with chemotherapy.