Gastrointestinal Stromal Tumors (GIST): A Prospective Analysis and an Update on Biomarkers and Current Treatment Concepts

Koumarianou, Anna; Economopoulou, Panagiota; Katsaounis, Panagiotis; Laschos, Konstantinos; Arapantoni-Dadioti, Petroula; Martikos, Georgios; Rogdakis, A.; Tzanakis, Νikolaos; Boukovinas, I.

doi:10.4137/bic.s25045

Cited by 13 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Gastrointestinalni stromalni tumor (GIST) rijedak je i čini svega 1 % tumora u gastrointestinalnom traktu (GIT), no najčešći je mezenhimalni tumor tog područja [1][2][3][4][5][6] . Po svojim patohistološkim karakteristikama nalikuje drugim tumorima iz skupine mezenhimalnih tumora (lejomiom, lejomiosarkom, švanom, sinovijalni sarkom) pa je imunohistokemija neophodna za postavljanje dijagnoze 6 .…”

Section: Uvodunclassified

“…Po svojim patohistološkim karakteristikama nalikuje drugim tumorima iz skupine mezenhimalnih tumora (lejomiom, lejomiosarkom, švanom, sinovijalni sarkom) pa je imunohistokemija neophodna za postavljanje dijagnoze 6 . GIST kao mezenhimalni tumor nastaje iz intersticijskih Cajalovih stanica 4,5,7 . Te su intersticijske stanice međusobno umrežene i umetnute između stanica glatkog mišićja GIT-a s kojima tvore dodir na mjesta slična sinapsama.…”

Section: Uvodunclassified

“…Cajalove intersticijske stanice ciklično mijenjaju svoj membranski potencijal uz pomoć posebnih ionskih kanala koji se otvaraju u pravilnim vremenskim razmacima, te tako nastaju predvodničke struje koje uzrokuju sporovalnu aktivnost čija frekvencija fiziološki određuje ritam većine gastrointestinalnih kontrakcija 7,8 . Epidemiološke studije pokazale su da se GIST javlja najčešće u starijoj životnoj dobi (statistički raspon godina u većini studija 60 -65) te da značajna razlika u incidenciji među spolovima ne postoji 1,4,6,9 . Ustanovilo se i da postoji obiteljska predispozicija koja se povezuje sa CD117 mutacijom (engl.…”

Section: Uvodunclassified

“…proto-oncogene c-KIT), koji normalno interferira s procesom diferencijacije Cajalovih stanica 2,4-6 . Najčešće su lokalizacije GIST-a želudac (oko 60 % u većini studija) 1,4,6,9 , a nakon toga tanko crijevo. Oko 1/4 tumora malignog je potencijala, dok su preostali benigni ili su nesigurnog malignog potencijala 1,6 .…”

Section: Uvodunclassified

“…Oko 1/4 tumora malignog je potencijala, dok su preostali benigni ili su nesigurnog malignog potencijala 1,6 . GIST se u pacijenata klinički može manifestirati kao abdominalni bol i nelagoda, akutno/kronično krvarenje sa ili bez posljedične anemije, slabost, mučnina, povraćanje, a rijetko i opstruktivnim tegobama 1,3,4,6 . Zbog vrlo nespecifične prezentacije obično se otkriva slučajno endoskopski, tijekom operacije ili pri kompjutoriziranoj tomografiji 6 .…”

Section: Uvodunclassified

See 4 more Smart Citations

Review of gastrointestinal stromal tumors and contribution of dog1 immunohistochemical marker in diagnostics: A single tertiary centerb experience

et al. 2017

View full text Add to dashboard Cite

Sažetak. Cilj: Prikazati patohistološko dijagnostičko iskustvo Kliničkog bolničkog centra (KBC)Rijeka u pacijenata s gastrointestinalnim stromalnim tumorom (GIST) dijagnosticiranim u razdoblju od 10 godina te pružiti pregled temeljnih karakteristika ovog mezenhimalnog tumora. Cilj je bio i prikazati osjetljivost DOG1 markera (engl. Discovered on GIST) te ga usporediti s osjetljivošću CD117 i vimentina. Materijali i metode: Iz baze podataka Zavoda za patologiju od 2005. do 2015. godine prikupljeni su podaci o 89 pacijenata s dijagnozom GIST-a. Podaci koje smo statistički analizirali obuhvaćali su dob, spol, lokalizaciju tumora, vrstu stanica (vretenaste ili epiteloidne), imunohistokemijske karakteristike te veličinu i mitotički indeks kao dva najvažnija parametra za određivanje prognostičke skupine. Rezultati: Medijan dobi iznosio je 64 godine, s rasponom od 17 do 93 godine. Značajna razlika u incidenciji među spolovima nije pronađena. Najčešća lokalizacija bio je želudac s postotkom od 48,3 %. Vretenastu morfologiju imalo je 84,3 % tumora, epiteloidnu 3.4 %, a miješanu (epiteloidno-vretenastu) 12,3 %. Podjelom GIST-ova u prognostičke skupine ustanovili smo da je 65,2 % tumora bilo benigno, 33,7 % maligno, a 1,1 % imalo je nesigurni maligni potencijal. Na uzorku od 25 tumora određivali smo osjetljivost imunohistokemijskih markera i dobili sljedeće rezultate: DOG1 imao je osjetljivost 100 %, CD117 88 %, a vimentin 60 %. Zaključci: DOG1 najosjetljiviji je imunohistokemijski marker korišten za GIST. Njegovo uvođenje u rutinsku imunohistokemijsku analizu pružilo je snažan doprinos u postavljanju dijagnoze. Prikazano iskustvo našeg centra moglo bi pružiti doprinos u napredovanju patološkodijagnostičke obrade GIST-ova na razini Republike Hrvatske.Ključne riječi: CD117 antigen; DOG1; gastrointestinalni stromalni tumori; imunohistokemija Abstract. Aim: To present the experience of Clinical Hospital Center (CHC) Rijeka, Department of Pathology in diagnosing gastrointestinal stromal tumors (GIST) in a 10-year period and to demonstrate consequential characteristics of this mesenchymal tumor. Also the aim was to present the sensitivity of DOG1 (Discovered on GIST) immunohistochemical marker, and to compare it with CD117 and vimentin results. Materials and methods: Searching the Pathology Department database, 89 GISTs were found in the period from 2005 to 2015. Epidemiologic and clinicopathological data: age, gender, dimension, localization, immunohistochemical charachteristics, also mitotic rate and malignant potential as two most important parameters for prognostic group estimation, were statistically analyzed. Results: Median age was 64, range from 17 to 93. 48.3 % of patients were male and 51.7 % were female. Most GISTs (48.3 %) were localized in stomach. Spindle cell morphology was present in 84.3 % GISTs, epitheloid in 3.4 % and mixed in 12.3 % tumors. According to the prognostic groups, malignant potential was assigned. The biggest portion, 65.2 % of tumors, were benign. Malignant potential was present

show abstract

Section: Uvodunclassified

See 3 more Smart Citations

Review of gastrointestinal stromal tumors and contribution of dog1 immunohistochemical marker in diagnostics: A single tertiary centerb experience

et al. 2017

View full text Add to dashboard Cite

show abstract

Comprehensive molecular screening by next generation sequencing reveals a distinctive mutational profile of KIT/PDGFRA genes and novel genomic alterations: results from a 20-year cohort of patients with GIST from north-western Greece

Mavroeidis

Metaxa-Mariatou²,

Papoudou‐Bai

et al. 2018

ESMO Open

View full text Add to dashboard Cite

IntroductionGastrointestinal stromal tumours (GIST) are mesenchymal neoplasms that usually carry an activating mutation in KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes with predictive and prognostic significance. We investigated the extended mutational status of GIST in a patient population of north-western Greece in order to look at geopraphic/genotypic distinctive traits.Patient and methodsClinicopathological and molecular data of 38 patients diagnosed from 1996 to 2016 with GIST in the region of Epirus in Greece were retrospectively assessed. Formalin-fixed paraffin-embedded tumours were successfully analysed for mutations in 54 genes with oncogenic potential. Next generation sequencing was conducted by using the Ion AmpliSeqCancer Hotspot Panel V.2 for DNA analysis (Thermofisher Scientific).ResultsAmong 38 tumours, 24 (63.16%) and seven (18.42%) of the tumours harboured mutations in the KIT and PDGFRA genes, respectively, while seven (18.42%) tumours were negative for either KIT or PDGFRA mutation. No mutations were detected in five (13.16%) cases. Concomitant mutations of BRAF and fibroblast growth factor receptor 3 (FGFR3) genes were observed in two patients with KIT gene mutation. Two patients with KIT/PDGFRA wild-type GIST had mutations in either KRAS or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) genes. There was no significant survival difference regarding the exonic site of mutation in either KIT or PDGFRA gene. The presence of a mutation in pathway effectors downstream of KIT or PDGFRA, such as BRAF, KRAS or PIK3CA, was associated with poor prognosis. Adverse prognosticators were also high mitotic index and the advanced disease status at diagnosis.ConclusionsWe report comparable incidence of KIT and PDGFRA mutation in patients with GIST from north-western Greece as compared with cohorts from other regions. Interestingly, we identified rare mutations on RAS, BRAF and PIK3CA genes in patients with poor prognosis.

show abstract

Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors

et al. 2019

View full text Add to dashboard Cite

Background: cKIT kinase overexpression and gain-of-function mutations are the critical pathogenesis of gastrointestinal stromal tumors (GISTs). Although the multiple kinase inhibitors such as imatinib, sunitinib, and regorafenib have been approved for GISTs, the acquisition of polyclonal secondary resistance mutations in KIT is still a limitation for GIST treatment. Here we explored the KIT inhibitory activity of axitinib in preclinical models and describe initial characterization of its activity in GIST patient-derived primary cells. Methods: The activities of axitinib against mutant KIT were evaluated using protein-based assay and a panel of engineered and GIST-derived cell lines. The binding modes of axitinib-KIT/KIT mutants were analyzed. Four primary cells derived from GIST patients were also used to assess the drug response of axitinib. Results: Axitinib exhibited potent activities against a variety of cKIT associated primary and secondary mutations. It displayed better activity against cKIT wild-type, cKIT V559D/A/G, and L576P primary gain-of-function mutations than imatinib, sunitinib, and regorafenib. In addition, it could inhibit imatinib resistant cKIT T670I and V654A mutants in vitro and in vivo GIST preclinical models. Conclusion: Our results provide the basis for extending the application of axitinib to GISTs patients who are unresponsive or intolerant to the current therapies.

show abstract

Gastrointestinal Stromal Tumors (GIST): A Prospective Analysis and an Update on Biomarkers and Current Treatment Concepts

Cited by 13 publications

References 47 publications

Review of gastrointestinal stromal tumors and contribution of dog1 immunohistochemical marker in diagnostics: A single tertiary centerb experience

Review of gastrointestinal stromal tumors and contribution of dog1 immunohistochemical marker in diagnostics: A single tertiary centerb experience

Comprehensive molecular screening by next generation sequencing reveals a distinctive mutational profile of KIT/PDGFRA genes and novel genomic alterations: results from a 20-year cohort of patients with GIST from north-western Greece

Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors

Contact Info

Product

Resources

About