Diffuse Mesothelin Expression Correlates with Prolonged Patient Survival in Ovarian Serous Carcinoma

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Abstract
Purpose: Mesothelin is an emerging marker for cancer diagnosis and target-based therapy, yet relatively little is known about the clinical significance of mesothelin expression in tumors. In this study, we correlate mesothelin immunoreactivity to clinicopathologic features in ovarian serous carcinoma. Experimental Design: Mesothelin expression levels were compared among 81 publicly available serial analysis of gene expression (SAGE) libraries of various carcinoma and normal tissue types. Immunohistochemistry using a well-characterized mesothelin monoclonal antibody (5B2) was done to evaluate mesothelin expression in 167 high-grade and 31 low-grade ovarian serous carcinomas. Immunohistochemistry staining scores were correlated with patient survival, tumor site, tumor grade, in vitro drug resistance, and differentiation status of tumor cells. Results: SAGE analysis showed that mesothelin was overexpressed in 50% of ovarian and pancreatic carcinomas but rarely in other cancer types, including liver, colon, kidney, prostate, and breast. Mesothelin immunoreactivity (>5% of tumor cells) was present in 55% of ovarian serous carcinomas with no difference in expression between high-grade and low-grade serous tumors (P = 0.82). Based on Kaplan-Meier analysis, we found that a diffuse mesothelin staining (>50% of tumor cells) in primary high-grade ovarian carcinomas correlated significantly with prolonged survival in patients who had advanced-stage disease and had received optimal debulking surgery followed by chemotherapy (P = 0.023). Mesothelin expression did not correlate significantly with patient age, tumor site, in vitro drug resistance, or tumor differentiation status (P > 0.10). Conclusion: Our results provided new evidence that mesothelin expression is associated with prolonged survival in patients with high-grade ovarian serous carcinoma.