Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis

Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.