Differential proliferative index of cancer stem-like cells in primary and recurrent medulloblastoma in human

Purpose Medulloblastoma is the most common malignant primitive neuroectodermal tumor found in children. It has a tendency to recur at a primary or distant site. The mechanism underlying the regulation of the recurrence of medulloblastoma remains largely unknown. Recently, several reports have described that cancer stem-like cells (CSCs) can be identified and isolated in medulloblastoma. The authors therefore attempted to demonstrate the correlation between the biological features of medulloblastoma's CSCs and its recurrence Methods The data used were obtained in five consecutive patients with medulloblastomas who subsequently experienced tumor recurrence from 2004 to 2007. The authors performed the immunohistochemical assays to analyze the expression of CSC markers, proliferation features, and proliferative status of CSCs in primary and recurrent medulloblastoma. Results Of the five patients, two had recurrence at the primary site and three had a distant recurrence. CSC markers such as CD133(Prominin-1), DCX, PSA-NCAM, TUC-4, and nestin were expressed regardless of primary or recurrent medulloblastoma. All the five tumor specimens had a high proliferation index (PI). The PI was even higher in the group of patients after recurrence at a distant site (p<0.05), while the PI remained almost the same after primary recurrence. The Ki67/nestin-, Ki67/DCX-, and Ki67/TUC-4-positive cells were significantly increased in recurrent medulloblastoma at both the primary and distant sites, whereas CSCs in primary medulloblastoma showed much lower proliferative features (p<0.05). Conclusions Our data suggest that tumorigenesis of medulloblastomas and their recurrence might be related to CSCs. More proliferating CSCs in medulloblastomas denote worse prognosis.