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dc.date.accessioned2013-03-12T08:39:22Z
dc.date.issued2010en_US
dc.date.submitted2010-09-07en_US
dc.identifier.citationHøland, Maren. Prognostic value of protein markers in malignant peripheral nerve sheath tumours. Masteroppgave, University of Oslo, 2010en_US
dc.identifier.urihttp://hdl.handle.net/10852/11430
dc.description.abstractMalignant peripheral nerve sheath tumour (MPNST) is a rare and highly aggressive malignancy with high frequency of both local recurrence and distant metastasis. About half of all cases arise in individuals with the hereditary disease neurofibro-matosis type 1 (NF1), while the rest are sporadic cases. The five-year survival rate for patients with MPNST is reported between 30% and 50% and the current knowledge of prognostic markers in MPNST remains limited. Identification of molecular markers with prognostic value at time of MPNST surgery may aid in choice of treatment strategy and in improving the management of these patients. MPNST typically have highly complex karyotypes and some recurrent aberrations are found. It is likely that genes and proteins affected by these changes contribute to development of MPNST. In this study, we have selected genes within regions of copy number changes as well as genes that are highly expressed in the malignant tumours compared to the benign neurofibromas, and tested the in situ expression of the encoded proteins by immunohistochemistry in a series of Norwegian and Swedish MPNSTs included in a tissue microarray (TMA). The TMA consisted of MPNST samples from 64 patients for which follow up data were available. We found several proteins that were associated with disease specific survival, and identified a new three-protein expression profile, where the combination of BIRC5, EGFR, and TOP2A showed strong prognostic information for patients with MPNST (P=6x10-5). The combined protein expression status was independent of the remission status of the patient after surgery, which was the strongest clinical marker for survival. In fact, among the patients in complete remission, those with high expression of at least two of the three proteins BIRC5, EGFR, or TOP2A in their tumours had a hazard rate for MPNST related death within ten year that was more than five times higher than for patients with high expression of none or only one of the markers. The three-protein expression profile was significantly associated with survival of patients with NF1, as well as of patients with sporadic disease, however, the association was strongest for patients with NF1. Special attention was given to proteins encoded by genes that map to loci on chromosome arm 17q, that in whole or in part is gained in 70% of MPNST. The in situ expression of BIRC5, TK1, and/or TOP2A showed a significant correlation with poor prognosis, and increasing level of expression correlated with decreasing survival rate (P=0.001). This association was independent of remission status, and was significant for patients with NF1, but not for patients with sporadic disease.eng
dc.language.isoengen_US
dc.titlePrognostic value of protein markers in malignant peripheral nerve sheath tumoursen_US
dc.typeMaster thesisen_US
dc.date.updated2011-03-28en_US
dc.creator.authorHøland, Marenen_US
dc.date.embargoenddate10000-01-01
dc.rights.termsDette dokumentet er ikke elektronisk tilgjengelig etter ønske fra forfatter. Tilgangskode/Access code Aen_US
dc.rights.termsforeveren_US
dc.subject.nsiVDP::473en_US
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Høland, Maren&rft.title=Prognostic value of protein markers in malignant peripheral nerve sheath tumours&rft.inst=University of Oslo&rft.date=2010&rft.degree=Masteroppgaveen_US
dc.identifier.urnURN:NBN:no-26056en_US
dc.type.documentMasteroppgaveen_US
dc.identifier.duo105253en_US
dc.contributor.supervisorMatthias Kolberg, Ragnhild A. Lotheen_US
dc.identifier.bibsys101476809en_US
dc.rights.accessrightsclosedaccessen_US
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/11430/2/Masteroppgaven_MarenHoeland.pdf


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