title: Survivin expression and prognostic significance in pediatric malignant peripheral nerve sheath tumors (MPNST).
abstract: Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5-10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions.
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Turrini
authors.forename: Daniela
authors.initials: D
authors.lastname: Boldrin
authors.forename: Anna
authors.initials: A
authors.lastname: Merlo
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dall'igna
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Coffin
authors.forename: Annalisa
authors.initials: A
authors.lastname: Martines
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaldi
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: De Salvo
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009367:Neoplasm Staging; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin