Značaj mutacija u genima KIT i PDGFRA u evaluaciji lečenja bolesnika operisanih zbog gastrointestinalnog stromalnog tumora želuca
Significance of KIT and PDGFRA gene mutation in evaluation of surgically treated gastric gastrointestinal stromal tumor patients
Author
Ebrahimi, Keramatollah A.Mentor
Peško, PredragCommittee members
Novaković, Ivana
Sabljak, Predrag
Čolović, Radoje
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Show full item recordAbstract
Cilj: Ispitivanje genetskih mutacija na KIT i PDGFRA genima, prikazivanje njihove učestalosti, vrste
mutacija i korelacije ovih specifičnih genskih mutacija sa patohistološkim i imunohistohemijskim
karakteristikama tumora. Korelacija genetskih mutacija na KIT i PDGFRA sa kliničkim tokom operisanih
bolesnika.
Metod: Prospektivna i delimično retrospektivna klinička studija koja je uključila 100 bolesnika operisane
zbog GIST-a želuca u period od 2005 do 2016 godine. Načinjena je molekularna analiza na parafinskim
kalupima tumorskog tkiva, a kod 45 bolesnika kod kojih su identifikovane KIT i PDGFRA mutacije
sprovedena je dalja analiza, sa posebnim osvrtom na patološke karakteristike tumora, recidiv oboljenja i
ukupno preživljavanje, te procena uticaja analiziranih genskih mutacija na navedene promene.
Rezultati: Od 100 operisanih bolesnika 46% su u grupi visokog rizika od kojih kod 54% nastaju
metastaze ili lokalni recidiv. Od ukupno 100 ispitivanih bolesnika, kod 45 bolesnika je dobijen m...utacioni
status, gde su 37 (82%) bolesnika sa KIT mutacijama, 6 (14%) bolesnika sa PDGFRA mutacije i 2 (4%)
bolesnika svrstani u "wild type". Analizom krive preživljavanja kod bolesnika operisanih zbog GIST
želuca utvrđena je značajna razlika u javljanju metastaze i smrtnog ishoda u zavisnosti od tipa
mutacije(p=0.023). Cox-ovim regresionom analizom je pokazano da bolesnici visokog rizika sa
recidivom bolesti koji nisu primali Imatinib imali su 7 puta veću verovatnoću smrtnog ishoda u odnosu na
bolesnike lečene Imatinobom
Zaključak: Analiza mutacije na KIT i PDGFRA genima ima prognostički i prediktivni značaj kod
bolesnika operisanih zbog GIST želuca. Imatinib ima značajnu ulogu u lečenju bolesnika koji su u grupi
viskog rizika.
Objective: KIT (KIT proto-oncogene receptor tyrosine kinase) and PDGFRA (Platelet derived growth
factor receptor alpha) gene mutations represent major molecular forces inside the gastrointestinal stromal
tumors (GIST). Aim of this study was to evaluate these mutations in patients who underwent surgical
resection of gastric GIST
Methods: Retrospective clinical study included 100 patients who were operated due to gastric GIST from
2005 till 2016. Molecular analysis of paraffin embedded tumor tissue was performed, and the 45 patients
who had presence of KIT and PDGFRA mutations were further evaluated, with regard to pathological
tumor stage, disease recurrence and overall survival.
Results: Of the 100 patients who were operated 46% are in the high risk group of which at 54% of the
resulting metastasis or local recurrence. From a total of 100 patients, in 45 patients we obtained
mutational status, where 37 (82%) of patients had KIT mutations, 6 (14%) patients had PDGFRA
mutations and 2 (4%...) patients were classified into the “ wild-type”. The analysis of survival curves in
patients surgically treated for gastric GIST showed a significant difference in emergence of metastases
and death depending on the type of mutation (p = 0.023). Cox's regression analysis shown that patients
with a high risk of recurrent disease who were not receiving Imatinib had the 7 times greater probability
of fatal outcome compared to patients treated with Imatinib.
Conclusion: Analysis of mutations in the genes KIT and PDGFRA has prognostic and predictive
significance in patients surgically treated for gastric GIST. Imatinib has an important role in the treatment
of patients who are in the group of high risk.