Medulloblastoma (MDB) is the most common malignant paediatric brain tumor. Prognostic system based on clinical parameters and histopathological variants is commonly used in clinical practice. Four different molecular subgroups are recognized: WNT and SHH, having specific homonymous pathwayalterations;Cand D, havingseveral genetic alterationsand associated to a worse outcome, but the system has not been prospectively validated in metastatic cohorts. Purpose of this studywasto evaluate distribution andprognostic impact of the four molecular subgroups in 47 MDB metastatic at the onset, homogenously treated in a single institution (Gandola et al, JCO 2009). Subgroup biomarkers were investigated by IHC, RT-PCR, mRNA sequencing, FISH; results were correlated with patient outcomes by Kaplan-Meier. We identify 11% WNT with nuclear b-catenin, 19% SHH, 26%groupCand15%group D;29%were unclassifiable (NC) having heterogeneous biomarkers. MYC amplification was more frequent (32.5%) compared to MYCN (2.7%). WNT and NC groups showed longer (not significant) OSand PFS compared to SHH,Cand D. Furthermore, low expression of FSTL5 was associated with good prognosis (OS rate 90%, PFS rate 100%), while FSTL5 higher expression correlate with worse outcome (OS and PFS rate 66%); difference was statistically significant (p ¼ 0,05). We have previously shown that histological variants maintain prognostic value in metastatic MDB; on the opposite, molecular sub-grouping is inefficient to allow a better risk stratification in our metastatic MDB cohort; furthermore, FSTL5 gene expression might be used in metastatic MDB as prognostic factor to better define patient outcome.
Distribution and prognostic impact of molecular subgroups in a homogeneously treated series of metastatic medulloblastoma / Romana Buttarelli, Francesca; Giangaspero, Felice; Minasi, Simone; Antonelli, Manila; Massimino, Maura. - In: NEURO-ONCOLOGY. - ISSN 1522-8517. - 18:Suppl. 3(2016). (Intervento presentato al convegno International Symposium on Pediatric Neuro-Oncology tenutosi a Liverpool; UK) [10.1093/neuonc/now076.72].
Distribution and prognostic impact of molecular subgroups in a homogeneously treated series of metastatic medulloblastoma
Romana Buttarelli, Francesca;GIANGASPERO, FELICE;MINASI, SIMONE;ANTONELLI, MANILA;
2016
Abstract
Medulloblastoma (MDB) is the most common malignant paediatric brain tumor. Prognostic system based on clinical parameters and histopathological variants is commonly used in clinical practice. Four different molecular subgroups are recognized: WNT and SHH, having specific homonymous pathwayalterations;Cand D, havingseveral genetic alterationsand associated to a worse outcome, but the system has not been prospectively validated in metastatic cohorts. Purpose of this studywasto evaluate distribution andprognostic impact of the four molecular subgroups in 47 MDB metastatic at the onset, homogenously treated in a single institution (Gandola et al, JCO 2009). Subgroup biomarkers were investigated by IHC, RT-PCR, mRNA sequencing, FISH; results were correlated with patient outcomes by Kaplan-Meier. We identify 11% WNT with nuclear b-catenin, 19% SHH, 26%groupCand15%group D;29%were unclassifiable (NC) having heterogeneous biomarkers. MYC amplification was more frequent (32.5%) compared to MYCN (2.7%). WNT and NC groups showed longer (not significant) OSand PFS compared to SHH,Cand D. Furthermore, low expression of FSTL5 was associated with good prognosis (OS rate 90%, PFS rate 100%), while FSTL5 higher expression correlate with worse outcome (OS and PFS rate 66%); difference was statistically significant (p ¼ 0,05). We have previously shown that histological variants maintain prognostic value in metastatic MDB; on the opposite, molecular sub-grouping is inefficient to allow a better risk stratification in our metastatic MDB cohort; furthermore, FSTL5 gene expression might be used in metastatic MDB as prognostic factor to better define patient outcome.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
