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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Lack of microsatellite instability in gastrointestinal stromal tumors

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Author(s):
Campanella, Nathalia C. [1] ; Scapulatempo-Neto, Cristovam [2, 1] ; Abrahao-Machado, Lucas Faria [2] ; Torres De Oliveira, Antonio Talvane [3] ; Berardinelli, Gustavo N. [1] ; Guimaraes, Denise Peixoto [1, 4] ; Reis, Rui M. [1, 5, 6]
Total Authors: 7
Affiliation:
[1] Barretos Canc Hosp, Mol Oncol Res Ctr, 1331 Antenor Duarte Vilela St, BR-14784400 Barretos, SP - Brazil
[2] Barretos Canc Hosp, Dept Pathol, BR-14784400 Barretos, SP - Brazil
[3] Barretos Canc Hosp, Dept Surg, BR-14784400 Barretos, SP - Brazil
[4] Barretos Canc Hosp, Dept Endoscopy, BR-14784400 Barretos, SP - Brazil
[5] Univ Minho, Hlth Sci Sch, Life & Hlth Sci Res Inst, P-4704553 Braga - Portugal
[6] Univ Minho, Life & Hlth Sci Res Inst, PT Govt Associate Lab 3Bs, P-4704553 Braga - Portugal
Total Affiliations: 6
Document type: Journal article
Source: Oncology Letters; v. 14, n. 5, p. 5221-5228, NOV 2017.
Web of Science Citations: 2
Abstract

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 a (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. (AU)

FAPESP's process: 13/25787-3 - Study of biomarkers of prognosis and response to therapy in gastrointestinal stromal tumors (GISTs)
Grantee:Nathália Cristina Campanella
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)