Gastrointestinal Stromal Tumors: Key to Diagnosis and Choice of Therapy

Overview

Journal Mol Diagn Ther

Specialties Molecular Biology
Pathology
Pharmacology

Date 2008 May 31

PMID 18510377

Citations 11

Authors

Piotr Rutkowski

Maria Debiec-Rychter

Wlodzimierz Ruka

Affiliations

Soon will be listed here.

Abstract

The common feature of gastrointestinal stromal tumors (GISTs) is the expression of KIT protein or acquisition of activating, constitutive mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes that are the early oncogenic events during GIST development. With these discoveries, GIST has emerged as a distinct sarcoma entity, enabling the introduction of targeted therapy using the inhibition of KIT/PDGFRA and their downstream signaling cascade. The introduction of a small-molecule tyrosine kinase inhibitor, imatinib mesylate, to clinical practice has revolutionized the treatment of patients with advanced GISTs and is currently approved as first-line treatment for patients with metastatic and/or inoperable GISTs. Mutation screening is currently a tool in GIST diagnosis, assessment of sensitivity to tyrosine kinase inhibitors, and prediction of achieving response to molecularly targeted therapy. This article discusses the histologic and molecular criteria for distinguishing GISTs from other types of sarcoma, and the molecular diagnostic tools that are currently available or in development to assist in therapy decisions.

Citing Articles

Endoscopic ultrasound-guided cutting of holes and deep biopsy for diagnosis of gastric infiltrative tumors and gastrointestinal submucosal tumors using a novel vertical diathermic loop.

Liu Y, Yang X World J Gastroenterol. 2017; 23(15):2795-2801.

PMID: 28487617 PMC: 5403759. DOI: 10.3748/wjg.v23.i15.2795.

Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib.

Ramaswamy A, Jain D, Sahu A, Ghosh J, Prasad P, Deodhar K J Gastrointest Oncol. 2016; 7(4):624-31.

PMID: 27563454 PMC: 4963379. DOI: 10.21037/jgo.2016.03.13.

Role of surgery in patients with focally progressive gastrointestinal stromal tumors resistant to imatinib.

Gao X, Xue A, Fang Y, Shu P, Ling J, Qin J Sci Rep. 2016; 6:22840.

PMID: 26946961 PMC: 4780000. DOI: 10.1038/srep22840.

Genomic mapping of pathways in endometrial adenocarcinoma and a gastrointestinal stromal tumor located in Meckel's diverticulum.

Englert-Golon M, Budny B, Burchardt B, Wrotkowska E, Ziemnicka K, Ruchala M Oncol Lett. 2016; 11(2):1007-1015.

PMID: 26893683 PMC: 4734229. DOI: 10.3892/ol.2015.4004.

Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in north China.

Hao M, Zhao G, Du X, Yang Y, Yang J Tumour Biol. 2016; 37(8):10339-48.

PMID: 26846098 DOI: 10.1007/s13277-016-4914-4.

References

Singer S, Rubin B, Lux M, Chen C, Demetri G, Fletcher C . Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol. 2002; 20(18):3898-905. DOI: 10.1200/JCO.2002.03.095. View

Perez E, Livingstone A, Franceschi D, Rocha-Lima C, Lee D, Hodgson N . Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors. J Am Coll Surg. 2006; 202(4):623-9. DOI: 10.1016/j.jamcollsurg.2006.01.002. View

Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S . Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998; 279(5350):577-80. DOI: 10.1126/science.279.5350.577. View

Crosby J, Catton C, Davis A, Couture J, OSullivan B, Kandel R . Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol. 2001; 8(1):50-9. DOI: 10.1007/s10434-001-0050-4. View

Lasota J, Miettinen M . KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol. 2006; 23(2):91-102. DOI: 10.1053/j.semdp.2006.08.006. View

Verweij J, Casali P, Zalcberg J, Lecesne A, Reichardt P, Blay J . Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004; 364(9440):1127-34. DOI: 10.1016/S0140-6736(04)17098-0. View

Kawanowa K, Sakuma Y, Sakurai S, Hishima T, Iwasaki Y, Saito K . High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol. 2006; 37(12):1527-35. DOI: 10.1016/j.humpath.2006.07.002. View

Taniguchi M, Nishida T, Hirota S, Isozaki K, Ito T, Nomura T . Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res. 1999; 59(17):4297-300. View

Gutierrez J, Pita De Oliveira L, Perez E, Rocha-Lima C, Livingstone A, Koniaris L . Optimizing diagnosis, staging, and management of gastrointestinal stromal tumors. J Am Coll Surg. 2007; 205(3):479-91 (Quiz 524). DOI: 10.1016/j.jamcollsurg.2007.04.002. View

10.

Mol C, Dougan D, Schneider T, Skene R, Kraus M, Scheibe D . Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004; 279(30):31655-63. DOI: 10.1074/jbc.M403319200. View

11.

Choi H, Charnsangavej C, de Castro Faria S, Tamm E, Benjamin R, Johnson M . CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol. 2004; 183(6):1619-28. DOI: 10.2214/ajr.183.6.01831619. View

12.

Carney J, Stratakis C . Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet. 2002; 108(2):132-9. DOI: 10.1002/ajmg.10235. View

13.

Ernst S, Hubbs A, Przygodzki R, Emory T, Sobin L, OLeary T . KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest. 1999; 78(12):1633-6. View

14.

Guo T, Agaram N, Wong G, Hom G, DAdamo D, Maki R . Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res. 2007; 13(16):4874-81. DOI: 10.1158/1078-0432.CCR-07-0484. View

15.

Gunawan B, von Heydebreck A, Sander B, Schulten H, Haller F, Langer C . An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications. J Pathol. 2007; 211(4):463-70. DOI: 10.1002/path.2128. View

16.

Wong N, Young R, Malcomson R, Nayar A, Jamieson L, Save V . Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach. Histopathology. 2003; 43(2):118-26. DOI: 10.1046/j.1365-2559.2003.01665.x. View

17.

Wardelmann E, Losen I, Hans V, Neidt I, Speidel N, Bierhoff E . Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer. 2003; 106(6):887-95. DOI: 10.1002/ijc.11323. View

18.

Roberts K, Odell A, Byrnes E, Baleato R, Griffith R, Lyons A . Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Mol Cancer Ther. 2007; 6(3):1159-66. DOI: 10.1158/1535-7163.MCT-06-0641. View

19.

Miettinen M, El-Rifai W, H L Sobin L, Lasota J . Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 2002; 33(5):478-83. DOI: 10.1053/hupa.2002.124123. View

20.

Abrams T, Lee L, Murray L, Pryer N, Cherrington J . SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003; 2(5):471-8. View