Prognostic Impact of Cancer Stem Cell-Like Phenotypes in Pancreatic Ductal Adenocarcinoma

Aim: To investigate the expression of cancer stem cell-like phenotypes in invasive pancreatic ductal adenocarcinoma, we analysed the correlation between the expression status of stemness markers and minichromosome maintenance 2 (MCM2), and clinicopathological characteristics; we also evaluated the prognostic significance of cancer stem cell-like features. Methods and results: We performed immunohistochemical staining in 44 cases of invasive pancreatic ductal adenocarcinoma. Patients were classified into high-expression and low-expression groups on the basis of the expression level of CD133, CD44, ALDH1, EpCAM, and MCM2. Seventeen of the 44 cases (39%) demonstrated high expression levels of CD133, whereas 12 of the 44 cases (27%) demonstrated high expression levels of CD44; 36 of the 44 cases (81%) demonstrated high expression levels of ALDH1, and 21 of the 44 cases (47%) demonstrated high expression levels of EpCAM. MCM2 was expressed in the nuclei of cancer cells with a positive cell ratio that ranged from 10% to 70%. Frequent positive stemness markers and/or a low expression of MCM2 was significantly correlated with worse overall survival (P=0.030). We defined frequent positive stemness markers (number of highly expressed markers>3) and/or a low expression of MCM2 phenotypes as the representative pattern of a cancer stem cell-like phenotype. The cancer stem cell-like phenotype was identified as an independent factor of overall survival by univariate (P=0.03) and multivariate analysis (hazard ratio, 2.763%; 95% confidence interval, 1.121-6.813; P=0.0273). Conclusion: The cancer stem cell-like phenotype could be involved in therapeutic resistance, resulting in worse overall survival. The cancer stem cell-like phenotype can be an indicator of recurrence in cases of invasive pancreatic ductal adenocarcinoma.