Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome.

Background: Medulloblastoma has been classified into four core subgroups according to the transcriptional profile in recent years. However, some disagreement among researchers remains regarding the prognoses and most effective treatments of the different subgroups with different age distributions. Objective: To analyze medulloblastoma prognosis in children population based on four molecular subgroups classification. Methods: From January 2011 to January 2013, 84 consecutive medulloblastoma patients aged underwent tumor removal at Beijing Tiantan Hospital. A total of 55 patients who ranged in age from 4-18 years underwent detailed follow-up. Molecular subgrouping was performed using RT-PCR. Results: The two-year progression free survival (PFS) and overall survival (OS) rates for the entire cohort were 76.2±5.8% and 81.8±5.2%, respectively. Univariate analysis revealed that the Group 4 patients had a better survival (two-year OS, 90.6±5.2%) than the SHH subgroup (P=0.002) and Group 3 patients (P=0.008). Only 2 of the 23 nonmetastasized Group 4 patients relapsed, and chemotherapy did significantly affect these patients (PFS, P=0.685). One out of five WNT patients had tumor relapse and died at last. LC/A histology and chemotherapy were independent risk factors in multivariate analysis. Conclusions: In our study, the nonmetastasized Group 4 patients had an excellent prognosis. The SHH subgroup and Group 3 patients had worst prognoses. LC/A histology had a dismal prognosis in our cohorts which warrants intensive treatment.