Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

Mesothelin (MSLN) is a glycophosphatidylinositol(GPI)‑linked cell surface protein that is highly expressedin several types of malignant tumor, including malignantpleural mesothelioma, ovarian cancer and pancreaticadenocarcinoma. Recently, a comprehensive immunohistochemicalstudy using MN‑1 monoclonal antibody identifieda significant number of colorectal tumors in which MSLNwas expressed. However, the clinicopathological profiles andsurvival of patients with MSLN‑positive colorectal cancerhave not been fully analyzed. In the current study, the expressionof MSLN in 270 primary and 44 metastatic colorectaltumors was immunohistochemically analyzed to determinethe clinical usefulness of MSLN immunohistochemistryand to identify potential candidates for future anti‑MSLNtherapy. In vitro experiments using colon cancer cell lineswere performed to investigate the biological significanceof MSLN expression in tumors. The results of univariateanalyses identified a significant correlation between MSLNexpression and females (P=0.0042). Furthermore, an inversecorrelation between MSLN expression and solid/sheet‑likeproliferation (P=0.014) was also revealed. Additionally,overall survival was significantly shorter in patientswith diffuse luminal/membranous expression of MSLN(P=0.018). Multivariable Cox hazards regression analysisrevealed diffuse MSLN expression (hazard ratio, 2.26; 95%confidence interval, 1.04‑4.91; P=0.039) as a potential riskfactor. When comparing primary CRCs and the metastasisof each, a weakly positive correlation was identified forMSLN positivity (% positive cells; R=0.484; P<0.0001). Thein vitro experiments revealed a positive role for MSLN incolon cancer cell proliferation. Thus, MSLN immunohistochemistrymay be useful in the prognostication of patientswith CRC. The results demonstrated that significant numbersof patients with MSLN‑positive CRC exhibiting metastasiscould be targeted by anti‑MSLN therapies.