A novel role of cyclinD1 and p16 in clinical pathology and prognosis of childhood medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor in children. CyclinD1 is strongly implicated in the control of G1 progression and the phosphorylation of the retinoblastoma protein; p16 could specifically interact with cyclinD1 to inhibit the activity of cyclin-dependent kinase 4. The purpose of this study was to investigate whether quantitative assessment of cyclinD1 and p16 may predict the clinical prognosis in MB. We analyzed the expression of cyclinD1 and p16 antigens in a series of 42 MB with various grades and pathological types by immunohistochemical analysis on paraffin-embedded sections. Then, the correlation of cyclinD1 and p16 expression patterns with clinical-pathological features of patients and their prognostic relevance were determined. Compared with the normal cerebellum, expression of cyclinD1 in MB was significantly higher [69.05% (29/42) vs. 9.5% (4/42), P = 0.002], expression of p16 was significantly lower [42.9% (18/42) vs. 85.7% (36/42), P = 0.01]. CyclinD1 expression in MB was up-regulated in metastatic stage (P = 0.01), pathological type (P = 0.02), necrosis (P = 0.009), differentiation level (P = 0.01) as well as with differentiation direction (P = 0.03); p16 expression in MB was down-regulated with metastatic stage (P = 0.01), pathology type (P = 0.02), necrosis (P = 0.009) as well as with differentiation level (P = 0.01); negative significant correlation between p16 immunostaining and cyclinD1 was observed in MB (rs = −0.36, P = 0.02). We also found a statistically significant relationship between the percent of cyclinD1-positive cells and p16-positive cells in the tumors and clinical outcome, with higher levels of cyclinD1 and lower levels of p16 correlating with a worse prognosis. CyclinD1 and p16 may be independent biomarkers for clinical prognosis in MB. A combined detection of cyclinD1+/p16− expression may benefit us in prediction of a poor survival of MB.