title: High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma.
abstract: The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative- polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.
authors.affiliation: Neurosurgery Unit, Giannina Gaslini Children's Research Hospital, Genoa, Italy. rasoale@yahoo.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Raso
authors.forename: Samantha
authors.initials: S
authors.lastname: Mascelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Biassoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ugolotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Milanaccio
authors.forename: Sara
authors.initials: S
authors.lastname: Pignatelli
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferraro
authors.forename: Marco
authors.initials: M
authors.lastname: Pavanello
authors.forename: Marcello
authors.initials: M
authors.lastname: Ravegnani
authors.forename: Armando
authors.initials: A
authors.lastname: Cama
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Garrè
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger