CD133 expression in cancer cells predicts poor prognosis of non-mucin producing intrahepatic cholangiocarcinoma

Background: CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangiocarcinoma (ICC). Methods: Fifty-seven non-mucin producing ICC patients were enrolled in this study. Immunohistochemistry (IHC) and immunofluorescence staining for CD133 as well as other cancer-associated proteins, including cytokeratin 19, TGF-beta 1, p-Smad2 and epithelial-mesenchymal transition (EMT) markers S100A4, E-Cadherin and Vimentin were analyzed. Results: IHC staining showed that tumor cells in 52.6% of patients expressed CD133. The CD133(+) patients had significantly higher metastasis rate than those without CD133(+) tumor cells (36.7% vs. 10.1%, p = 0.03). The CD133(+) patients had shorter overall and disease-free survival time as compared to the CD133(-) patients. Furthermore, 90.9% of CD133(+) patients developed cancer recurrence, as compared to 64.3% of CD133(-) patients (p = 0.02). As compared to CD133(-) patients, tumor cells in CD133(+) patients demonstrated high levels of TGF-beta/p-Smad2 as well as EMT-like alteration, characterized by loss of E-Cadherin and expression of Vimentin and S100A4. Conclusions: CD133 expression in ICC tumor cells indicates poor prognosis of the disease and might be associated with TGF-beta related EMT alterations.