CD133 expression in well-differentiated pancreatic neuroendocrine tumors: A potential predictor of progressive clinical courses

Summary The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; WHO grades 1 and 2) and establish its clinical relevance using two separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into G1 and G2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than those with CD133− tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than CK19− cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of G1 and G2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 out of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and WHO grading may assist in stratifying patients in terms of the risk of progressive clinical courses.