Skip to main content
SpringerLink
Log in

Actualités sur les tumeurs stromales (GIST) de l’intestin grêle

Gastrointestinal Stromal Tumours (GIST) of small bowel: an update

  • Dossier Thématique / Thematic File
  • Published:
Côlon & Rectum

Résumé

Les tumeurs stromales gastro-intestinales (GIST) représentent une entité nosologique largement méconnue jusqu’en 1998, date à laquelle le rôle majeur de KIT a été mis en évidence. Très rapidement après, une thérapie ciblée, l’imatinib a permis de complètement modifier le pronostic des formes avancées. Environ 25–30% des GIST sont localisées dans le grêle. Le diagnostic de GIST repose sur l’examen histologique avec mise en évidence de l’expression de KIT. Des mutations de KIT ou PDGFRA sont présentes dans 85% des GIST. Elles ont une valeur théranostique. La chirurgie d’exérèse R0 sans effraction de la tumeur est le seul traitement potentiellement curatif des formes localisées. Un traitement adjuvant par imatinib est indiqué en cas de risque significatif de rechute métastatique. D’autres inhibiteurs de tyrosine-kinase ont déjà montré leur efficacité en cas d’échappement à l’imatinib dans les GIST métastatiques.

Abstract

Nosology of Gastrointestinal Stromal Tumours (GIST) changed significantly with the identification of the molecular basis of GIST, particularly KIT in 1998. The prognosis of advanced GISTs was then dramatically improved by the discovery of a targeted therapy by imatinib. Around 25% of GISTs are located in the small bowel. Diagnosis is based on histology and expression of KIT by immunochemistry. Mutations in KIT or PDGFRA are detected in 85% of cases. Surgical resection (R0) without perforation is the only potentially curative treatment in localized GISTs. Adjuvant therapy by imatinib is recommended in patients with significant risk of recurrence. Other tyrosine-kinase inhibitors have already showed efficacy in patients with secondary resistance to imatinib.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Références

  1. Hirota S, Isozaki K, Moriyama Y, et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279:577–580

    Article  CAS  PubMed  Google Scholar 

  2. Joenssu H, Roberts PJ, Sarlomo-Rikala M, et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056

    Article  Google Scholar 

  3. Emile JF, Brahimi S, Coindre JM, et al (2012) Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs. Med Oncol Sep 29:1765–1772

    Article  CAS  Google Scholar 

  4. Bilimoria KY, Bentrem DJ, Wayne JD, et al (2009) Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 249:63–71

    Article  PubMed  Google Scholar 

  5. Nilsson B, Bümming P, Meis-Kindblom JM, et al (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 103:821–829

    Article  PubMed  Google Scholar 

  6. Agaimy A, Wünsch PH, Hofstaedter F, et al (2007) Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol 31:113–120

    Article  PubMed  Google Scholar 

  7. Bachet JB, Emile JF. (2010) Diagnostic criteria, specific mutations and genetic predisposition in gastrointestinal stromal tumors (GISTs). Applic Clin Genet 3:1–17

    Google Scholar 

  8. Miettinen M, Fetsch JF, Sobin LH, Lasota J. (2006) Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30:90–96

    Article  PubMed  Google Scholar 

  9. Pasini B, McWhinney SR, Bei T, et al (2008) Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 16:79–88

    Article  CAS  PubMed  Google Scholar 

  10. Bachet JB, Landi B, Laurent-Puig P, et al (2013) Diagnosis, prognosis and treatment of patients with gastrointestinal stromal tumour (GIST) and germline mutation of KIT exon 13. Eur J Cancer May 3 [Epub ahead of print]

    Google Scholar 

  11. Miettinen M, Wang ZF, Sarlomo-Rikala M, et al (2011) Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol 35:1712–1721

    Article  PubMed Central  PubMed  Google Scholar 

  12. Guidelines Working Group (2012) Gastrointestinal stromal tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23 Suppl 7:49–55

    Google Scholar 

  13. GIST (2013) Thésaurus National de Cancérologie Digestive. Disponible online sur wwwTNCD.org. Version du01/05/2013

    Google Scholar 

  14. Miettinen M, Makhlouf H, Sobin LH, Lasota J (2006) Gastrointestinal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol 30:477–489

    Article  PubMed  Google Scholar 

  15. Samaha E, Rahmi G, Landi B, Méatchi T, Cellier C (2009) Management of small bowel polyps. Gastroenterol Clin Biol 33:247–252

    Article  CAS  PubMed  Google Scholar 

  16. Landi B, Palazzo L (2009) The role of endosonography in submucosal tumours. Best Pract Res Clin Gastroenterol 23:679–701

    Article  PubMed  Google Scholar 

  17. Tirumani SH, Jagannathan JP, Krajewski KM, et al (2013) Imatinib and Beyond in Gastrointestinal Stromal Tumors: A Radiologist’s Perspective. Am J Roentgenol 201:801–810

    Article  Google Scholar 

  18. Emile JF, Scoazec JY, Coindre JM. (2009) Gastrointestinal stroma tumors (GIST): what is new in 2009? Ann Pathol 29:20–23

    Article  PubMed  Google Scholar 

  19. Coindre JM, Emile JF, Monges G, et al (2005) Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy Ann Pathol 25:358–385

    Article  PubMed  Google Scholar 

  20. Emile JF (2013) Gastrointestinal stromal tumors (GIST): at the forefront of targeted therapies]. Med Sci (Paris) 29:630–636

    Article  Google Scholar 

  21. Rubin BP, Heinrich MC, Corless CL. (2007) Gastrointestinal stromal tumour. Lancet 369:1731–1741

    Article  CAS  PubMed  Google Scholar 

  22. Colombo C, Ronellenfitsch U, Yuxin Z, et al (2012) Clinical, pathological and surgical characteristics of duodenal gastrointestinal stromal tumor and their influence on survival: a multi-center study. Ann Surg Oncol 19:3361–3367

    Article  CAS  PubMed  Google Scholar 

  23. Cavallaro G, Polistena A, D’Ermo G, et al (2012) Duodenal gastrointestinal stromal tumors: Review on clinical and surgical aspects. Int J Surg 10:463–465

    Article  CAS  PubMed  Google Scholar 

  24. Duffaud F, Meeus P, Bchert JB, Cassier P, et al (2014) Conservative surgery vs. duodeneopancreatectomy in primary duodenal Gastrointestinal Stromal Tumors (GIST): A retrospective review of 114 patients from the French Sarcoma Group. Ann Oncol (in press)

    Google Scholar 

  25. Miettinen M, Lasota J. (2006) Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 23:70–83

    Article  PubMed  Google Scholar 

  26. Joensuu H, Vehtari A, Riihimäki J, et al (2012) Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol 13:265–274

    Article  PubMed  Google Scholar 

  27. DeMatteo RP, Ballman KV, Antonescu CR, et al (2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebocontrolled trial. Lancet 373:1097–1104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Joensuu H, Eriksson M, Sundby Hall K, et al (2012) One versus Three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 307:1265–1272

    Article  CAS  PubMed  Google Scholar 

  29. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) (2010) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a metaanalysis of 1,640 patients. J Clin Oncol 28:1247–1253

    Article  PubMed Central  Google Scholar 

  30. Le Cesne A, Ray-Coquard I, Bui BN, et al (2010) Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 11:942–949

    Article  PubMed  Google Scholar 

  31. Blay JY, Pérol D, Le Cesne A. (2012) Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors. Ann Oncol 23:1659–1665

    Article  PubMed  Google Scholar 

  32. Demetri GD, van Oosterom AT, Garrett CR, et al (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338

    Article  CAS  PubMed  Google Scholar 

  33. Demetri GD, Reichardt P, Kang YK, et al (2013) Efficacity and safety of regorafenib for Advanced gastrointestinal stromal tumors after failure of ilatinib and sunitinib. An international, multicentre, randomized, placbo-controlled phase 3 trial. Lancet 381:295–302

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EA4340, Université de Versailles, 78000, Versailles, France

    J. -F. Emile

  2. Service de pathologie, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, 9, avenue Charles de Gaulle, 92104, Boulogne, France

    J. -F. Emile

  3. Service d’oncologie digestive, HEGP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 20, rue Leblanc, 75015, Paris, France

    B. Landi

Authors
  1. J. -F. Emile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Landi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J. -F. Emile or B. Landi.

About this article

Cite this article

Emile, J.F., Landi, B. Actualités sur les tumeurs stromales (GIST) de l’intestin grêle. Colon Rectum 8, 25–33 (2014). https://doi.org/10.1007/s11725-014-0511-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11725-014-0511-4

Mots clés

Keywords

Search

Navigation