Extracellular Matrix Metalloproteinase Inducer is a Negative Prognostic Factor of Pediatric Medulloblastoma

Abstract

Medulloblastoma (MB) is the most common embryonal CNS tumor of childhood. Its survival rates have significantly improved over the years due to developments in diagnostic techniques and therapeutic strategies. However, it is still an important cause of cancer-related deaths in children. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells. Therefore, the aim of this study was to investigate whether the expression patterns of EMMPRIN may predict the clinical prognosis in MB. EMMPRIN expression in a series of 56MB with various grades and pathological types was analyzed by immunohistochemical staining on paraffin-embedded sections. Then, the correlation of EMMPRIN expression patterns with clinical-pathological features of patients and its prognostic relevance were determined. Immunohistochemistry revealed that the positive expression rate of EMMPRIN in MB (75.0%, 42/56) was significantly higher than that in normal cerebellums (6.7%, 2/30, p < 0.001). In addition, EMMPRIN expression in MB was up-regulated in higher metastatic stage (p < 0.01), aggressive histopathological type (p < 0.005), necrosis (p < 0.01), as well as with undifferentiated tumor (p < 0.01). Furthermore, over-expression of EMMPRIN correlated significantly with poor prognosis (0.01 < p < 0.05) and represented an independent prognostic marker of overall survival on multivariate analysis (p = 0.01). Our study suggests that EMMPRIN expression was associated with the progression of MB and its over-activation may be an important predictor of poor survival in this patient cohort. Therefore, EMMPRIN may be regarded both as a prognostic factor and a therapeutic target for MB.