Clinicopathological Significance of Mesothelin Expression In Colorectal Cancer

Background:Colorectal cancer is one of the leading causes of cancer associated morbidity and mortality in the world. Mesothelin, a plasma membrane differentiation antigen, is expressed at varying degrees in several human cancers. Its expression is associated with unfavorable patient outcome. Aim:To determine the expression profile of mesothelin gene in colorectal cancer and to correlate its expression with other established prognostic parameters of colorectal carcinoma including patient survival. Patients and Methods:The subjects of the present study were 40 patients who underwent elective surgical resection for primary colorectal carcinoma.To evaluate prognostic significance of mesothelin, immunohistochemistry was used to assess the expression pattern of mesothelin protein in surgically resected, formalin-fixed, paraffin-embedded colorectal carcinoma specimens. Results:Mesothelin protein was seen mainly expressed in the cell membrane of colorectal carcinoma cells. Immunohistochemically, luminal membrane positive for mesothelin expression was identified in 40% ( 16 out of 40) of cases. No significant association was found between mesothelin immunoreactivity and patient?s age, gender, tumor location and tumor size (P? 0.05). A statistically significant correlation was observed between mesothelin expression and histopathologic grade ( P? 0.05). High level of mesothelin expression was noted in mesothelin-expressing colorectal tumors of high grade malignancy. Luminal membrane expression of mesothelin was significantly associated with lymph node metastasis. No significant correlation was detected between mesothelin expression and tumor stage. Positive mesothelin expression was significantly associated with poor disease free survival. Patients with mesothelin +ve tumors had a shorter overall survival as compared to patients with mesothelin –ve tumors, but the difference was not statistically significant ( P?0.05). Conclusion:Our results suggest that immunohistochemical evaluation of luminal membrane expression of mesothelin in colorectal carcinoma would be of clinical benefit not only as a prognostic factor, but also, as a predictive factor for the eligibility to mesothelin-targeting therapies in the future.