Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked
cell surface protein that is highly expressed in several types of malignant
tumor, including
malignant pleural mesothelioma,
ovarian cancer and pancreatic
adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1
monoclonal antibody identified a significant number of
colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive
colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic
colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN
therapy. In vitro experiments using
colon cancer cell lines were performed to investigate the biological significance of MSLN expression in
tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P=0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse
luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04-4.91; P=0.039) as a potential risk factor. When comparing primary
CRCs and the
metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in
colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting
metastasis could be targeted by anti-MSLN
therapies.