Lack of microsatellite instability in gastrointestinal stromal tumors

Campanella,Nathália   C.; Scapulatempo‑Neto,Cristovam; Abrahão‑Machado,Lucas Faria; Torres De Oliveira,Antônio Talvane; Berardinelli,Gustavo   N.; Peixoto Guimarães,Denise; Reis,Rui   M.

doi:10.3892/ol.2017.6884

Lack of microsatellite instability in gastrointestinal stromal tumors

Authors:
- Nathália C. Campanella
- Cristovam Scapulatempo‑Neto
- Lucas Faria Abrahão‑Machado
- Antônio Talvane Torres De Oliveira
- Gustavo N. Berardinelli
- Denise Peixoto Guimarães
- Rui M. Reis
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Affiliations: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784‑400, Brazil, Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo 14784‑400, Brazil, Department of Surgery, Barretos Cancer Hospital, Barretos, São Paulo 14784‑400, Brazil
Published online on: September 4, 2017 https://doi.org/10.3892/ol.2017.6884
Pages: 5221-5228
Copyright: © Campanella et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 α (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.

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