Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/48485

TitleLack of microsatellite instability in gastrointestinal stromal tumors
Author(s)Campanella, Nathália C.
Scapulatempo-Neto, Cristovam
Abrahão-Machado, Lucas Faria
Oliveira, Antônio Talvane Torres
Berardinelli, Gustavo N.
Guimarães, Denise Peixoto
Reis, R. M.
KeywordsGastrointestinal stromal tumor
Microsatellite instability
KIT
Platelet-derived growth factor receptor α, immunotherapy
Immunotherapy
Platelet-derived growth factor receptor α
Issue date2017
PublisherSpandidos Publications
JournalOncology Letters
Abstract(s)The microsatellite instability (MSI) phenotype may constitute an important biomarker for patient response to immunotherapy, particularly to anti-programmed death-1 inhibitors. MSI is a type of genomic instability caused by a defect in DNA mismatch repair (MMR) proteins, which is present mainly in colorectal cancer and its hereditary form, hereditary nonpolyposis colorectal cancer. Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA), which are oncogenes that predict the response to imatinib mesylate. In addition to KIT/PDGFRA mutations, other molecular alterations are important in GIST development. In GISTs, the characterization of the MSI phenotype is scarce and the results are not consensual. The present study aimed to assess MSI in a series of 79 GISTs. The evaluation of MSI was performed by pentaplex polymerase chain reaction comprising five markers, followed by capillary electrophoresis. The expression of MMR proteins was evaluated by immunohistochemistry. Regarding the KIT/PDGFRA/B-Raf proto-oncogene, serine/threonine kinase molecular profile of the 79 GISTs, 83.6% of the tumors possessed KIT mutations, 10.1% had PDGFRA mutations and 6.3% were triple wild-type. The mutated-PDGFRA cases were associated with gastric location and a lower mitotic index compared with KIT-mutated and wild-types, and these patients were more likely to be alive and without cancer. MSI analysis identified 4 cases with instability in one marker, however, additional evaluation of normal tissue and immunohistochemical staining of MMR proteins confirmed their microsatellite-stable nature. The results of the present study indicated that MSI is not involved in GIST tumorigenesis and, therefore, cannot serve as a biomarker to immunotherapy response in GIST.
TypeArticle
URIhttp://hdl.handle.net/1822/48485
DOI10.3892/ol.2017.6884
ISSN1792-1074
1792-1082
Publisher versionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662911/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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