Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. Subjects, Materials, and Methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. Results: High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p =.021) and peritoneal recurrence (p =.018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p =.001), OS (p =.001), and peritoneal recurrence (p =.002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p =.013) and diffuse/mixed type gastric cancer (p =.010). Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. Implications for Practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.
All Science Journal Classification (ASJC) codes
- Cancer Research