Značaj mutacija KIT i PDGFRA kod bolesnika operisanih zbog gastrointestinalnog stromalnog tumora želuca bez primene imatiniba

  • Keramatollah A Ebrahimi University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Predrag Sabljak University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Aleksandar P Simić University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Ognjan M Skrobić University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Dejan Veličković University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Vladimir Šljukić University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
  • Ivana Novaković University of Belgrade, Faculty of Medicine, Institute for Human Genetics, Belgrade, Serbia
  • Valerija Dobričić University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Institute of Neurology, Belgrade, Serbia
  • Marjan Micev University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Digestive Pathology, Belgrade, Serbia
  • Predrag Peško University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP180205048E
Ključne reči: gastrointestinalni stromalni tumori, geni, mutacija, hirurgija digestivnog sistema, procedure, neoplazme, metastaze, prognoza, preživljavanje

Sažetak


Apstrakt

 

Uvod/Cilj. KIT (KIT proto-oncogene receptor tyrosine kinase) i PDGFRA (Platelet-derived growth factor receptor alpha) genske mutacije predstavljaju osnovne molekularne promene u grupi gastrointestinalnih stromalnih tumora (GIST). Cilj ove studije bio je da se analiziraju KIT i PDGFRA mutacije u grupi bolesnika koji su operisani zbog primarnog GIST-a želuca, ali bez terapije imatinib mesilatom. Metode. Načinjena je retrospektivna klinička studija koja je uključila bolesnike operisane zbog GIST-a želuca u periodu od novembra 2000. do novembra 2016. godine. Načinjena je molekularna analiza na parafinskim kalupima tumorskog tkiva, a kod 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 ukupno 45 bolesnika, 43 bolesnika imala su prisutne mutacije na KIT i PDGFRA genima, dok su dva bolesnika klasifikovani kao “wild type” GIST. Po učinjenoj kurativnoj resekciji, 11 bolesnika je klasifikovano u grupu GIST-a niskog stepena, 8 u grupu srednjeg, a 26 bolesnika u grupu visokog rizika od metastaziranja. KIT mutacije su bile prisutne kod 37 bolesnika, najčešće u formi deleciji na egzonu 11. PDGFRA mutacije bile su prisutne kod 6 bolesnika. Prisustvo KIT mutacija imalo je visoku statističku korelaciju sa mitotiskim indeksom (p = 0,021). Nakon desetogodišnjeg praćenja, svi bolesnici iz grupe sa PDGFRA mutacijama su bili živi, dok je stepen preživljavanja bolesnika sa KIT mutacijama iznosio 71% (p = 0,31). Zaključak. Prisustvo KIT egzon 11 delecija kod bolesnika kod kojih je sprovedena primarna hirurška intervencija zbog GIST-a želuca povezana je sa visokim mitotskim indeksom i lošijem ukupnom preživ­lja­va­nju, ali bez statistički značajne razlike u odnosu na bolesnike kod kojih je bila prisutna PDGFRA mutacija. Ovi rezultati ukazuju na prognostički značaj u pravcu agresivnog ponašanja tumora.

Biografije autora

Keramatollah A Ebrahimi, University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia

opšti hirurg na Centru za hirurgiju jednjaka

Klinički asistent na Medicinskom fakultetu, Univerziteta u Beogradu

Predrag Sabljak, University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia

načelnik V odeljenja, Prve hirurške klinike

Docent na Medicinskom fakultetu Beograd

Marjan Micev, University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Digestive Pathology, Belgrade, Serbia

načelnik odeljenja patologije Klinike za digestivnu hirurgiju

Predrag Peško, University of Belgrade, Faculty of Medicine, Clinical Center of Serbia, First Surgical University Hospital, Department of Esophageal Surgery, Belgrade, Serbia

načelnik centra za hirurgiju jednjaka

redovni profesor na Medicinskom fakultetu

Univerzitet u Beogradu

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Objavljeno
2021/07/06
Broj časopisa
Vol. 76 Br. 12 (2019): Vojnosanit Pregl
Rubrika
Originalni članak