nach oben

Molecular Diagnosis & Therapy

Erschienen in:

01.05.2008 | Cancer

Gastrointestinal Stromal Tumors

Key to Diagnosis and Choice of Therapy

verfasst von: Dr Piotr Rutkowski, Maria Debiec-Rychter, Wlodzimierz Ruka

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

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 α (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.

Miettinen M, Lasota J. Gastrointestinal stromal tumors: definitions, clinical, histological, immunohistochemical and molecular genetic features and differential diagnosis. Virchows Arch 2001; 438: 1–12PubMedCrossRef

Miettinen M, El-Rifai WW, Sobin LH, et al. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol 2002; 33: 478–83PubMedCrossRef

Joensuu H. Gastrointestinal stromal tumor (GIST). Ann Oncol 2006; 17Suppl. 10: x280–6PubMedCrossRef

Miettinen M, Majidi M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur J Cancer 2002; 38Suppl. 5: S39–51PubMedCrossRef

Perez EA, Livingstone AS, Franceschi D, et al. Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors. J Am Coll Surg 2006; 202: 623–9PubMedCrossRef

Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005; 100: 162–8PubMedCrossRef

Kindblom LG, Meis KindBlom J, Bumming P, et al. Incidence, prevalence, phenotype and biologic spectrum of gastrointestinal stromal tumors (GIST): a population based study of 600 cases [abstract]. Ann Oncol 2003; 13: 157

Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. A population-based study in western Sweden. Cancer 2005; 103(4): 821–9PubMedCrossRef

Goettsch WG, Bos SD, Breekveldt-Postma N, et al. Incidence of gastrointestinal stromal tumours is underestimated: results of a nation-wide study. Eur J Cancer 2005; 41: 2862–72CrossRef

10.

Tryggvason G, Gislason HG, Magnusson MK, et al. Gastrointestinal stromal tumors in Iceland, 1990–2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005; 117(2): 289–93PubMedCrossRef

11.

Bumming P, Ahlman H, Andersson J, et al. Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours. Br J Surg 2006; 93: 836–43PubMedCrossRef

12.

Rutkowski P, Nowecki ZI, Michej W, et al. Risk criteria and prognostic factors for predicting recurrences after resection of primary gastrointestinal stromal tumors (GISTs). Ann Surg Oncol 2007 Jul; 14(7): 2018–27PubMedCrossRef

13.

Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006; 130(10): 1466–78PubMed

14.

Emory TS, Sobin LH, Lukes L, et al. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol 1999; 23: 82–7PubMedCrossRef

15.

Belics Z, Csapo Z, Szabo I, et al. Large gastroinestinal stromal tumor presenting as an ovarian tumor: a case report. J Reprod Med 2003; 48(8): 665–8

16.

Nowecki ZI, Rutkowski P, Lindner B, et al. Gastrointestinal stromal tumors localized in small intestine and diagnosed preoperatively as gynecological neoplasms [in Polish]. Gin Pol 2005; 76: 855–62

17.

Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998; 152: 1259–69PubMed

18.

Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279: 577–80PubMedCrossRef

19.

Suster S, Fletcher CD. Gastrointestinal stromal tumors with prominent signet-ring cell features. Mod Pathol 1996; 9: 609–13PubMed

20.

Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 2000; 13: 1134–42PubMedCrossRef

21.

Fletcher C, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002; 33: 459–65PubMedCrossRef

22.

Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol 2002; 10: 81–9PubMedCrossRef

23.

DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000, 58

24.

DeMatteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 2008 Feb 1; 112(3): 608–15PubMedCrossRef

25.

Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006; 23(2): 70–83PubMedCrossRef

26.

Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol 2000; 24: 211–22PubMedCrossRef

27.

Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29: 52–68PubMedCrossRef

28.

Miettinen M, Furlong M, Sarlomo-Rikala M, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. Am J Surg Pathol 2001; 25: 1121–33PubMedCrossRef

29.

Miettinen M, Kopczynski J, Makhlouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 2003; 27: 625–41PubMedCrossRef

30.

Miettinen M, Makhlouf H, Sobin LH, et al. Gastrointestinal stromal 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 2006; 30: 477–89PubMedCrossRef

31.

Carillo R, Candia A, Rodriguez-Peralto JL, et al. Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in gastrointestinal stromal tumors. Hum Pathol 1997; 28: 160–5CrossRef

32.

Ozguc H, Yilmazlar T, Yerci O, et al. Analysis of prognostic and immunohistochemical factors in gastrointestinal stromal tumors with malignant potential. J Gastrointest Surg 2005; 9: 418–29PubMedCrossRef

33.

Cunningham RE, Federspiel BH, McCarthy WF, et al. Predicting prognosis of gastrointestinal smooth muscle tumors: role of clinical and histologic evaluation, flow cytometry, and image cytometry. Am J Surg Pathol 1993; 17: 588–94PubMedCrossRef

34.

Liu FY, Qi JP, Xu FL, et al. Clinicopathological and immunohistochemical analysis of gastrointestinal stromal tumor. World J Gastroenterol 2006; 12: 4161–5PubMed

35.

Hu TH, Chuah SK, Lin JW, et al. Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwanese. World J Gastroenterol 2006; 12: 595–602PubMed

36.

Wong NA, Young R, Malcomson RD, et al. Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach. Histopathology 2003; 43: 118–26PubMedCrossRef

37.

Crosby JA, Catton CN, Davis A, et al. Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol 2001; 8: 50–9PubMedCrossRef

38.

Aparicio T, Boige V, Sabourin JC, et al. Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours. Eur J Surg Oncol 2004; 30: 1098–103PubMedCrossRef

39.

Ueyama T, Guo KJ, Hashimoto H, et al. A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors. Cancer 1992; 69: 947–55PubMedCrossRef

40.

Fujimoto Y, Nakanishi Y, Yoshimura K, et al. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer 2003; 6: 39–48PubMedCrossRef

41.

Miettinen M, Sarlomo-Rikala M, Kovatich AJ. Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours. Virchows Arch 1998; 433: 255–60PubMedCrossRef

42.

Plaat BEC, Hollema H, Molenaar WM, et al. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol 2000; 18: 3211–20PubMed

43.

Nakamura N, Yamamoto H, Yao T, et al. Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade. Hum Path 2005; 36: 828–37PubMedCrossRef

44.

Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors: report of the GIST Consensus Conference of 20-21 March 2004, under auspices of ESMO. Ann Oncol 2005; 16: 566–78PubMedCrossRef

45.

West RB, Corless CL, Chen X, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004 Jul; 165(1): 107–13PubMedCrossRef

46.

Miettinen M, Virolainen M, Sarlomo-Rikala M. Gastrointestinal stromal tumors: value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas. Am J Surg Pathol 1995; 2: 207–16CrossRef

47.

Ma CK, Amin MB, Kintanar E, et al. Immunohistologic characterization of gastrointestinal stromal tumors: a study of 82 cases compared with 11 cases of leiomyomas. Mod Pathol 1993; 6: 139–44PubMed

48.

Hirota S, Ohashi A, Nishida T, et al. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 2003; 125: 660–7PubMedCrossRef

49.

Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004; 22: 3813–25PubMedCrossRef

50.

Heinrich MC, Rubin BP, Longley BJ, et al. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 2002; 33: 486–95CrossRef

51.

Wozniak A, Sciot R, Guillou L, et al. Array CGH analysis in primary gastrointestinal stromal tumors: cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status. Genes Chromosomes Cancer 2007; 46: 261–76PubMedCrossRef

52.

Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: gastrointestinal stromal tumors. Cancer Genet Cytogenet 2002; 135: 1–22PubMedCrossRef

53.

Debiec-Rychter M, Lasota J, Sarlomo-Rikala M, et al. Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation with c-KIT gene mutation. Cancer Genet Cytogenet 2001; 128: 24–30PubMedCrossRef

54.

Bergmann F, Gunawan B, Hermanns B, et al. Cytogenetic and morphologic characteristics off gastrointestinal stromal tumors: recurrent rearrangement of chromosome 1 and losses of chromosomes 14 and 22 as common anomalies. Verh Dtsch Ges Pathol 1998; 82: 275–8PubMed

55.

Fukasawa T, Chong JM, Sakurai S, et al. Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor. Jpn J Cancer Res 2000; 91: 1241–9PubMedCrossRef

56.

El-Rifai W, Sarlomo-Rikala M, Andersson LC, et al. DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. Cancer Res 2000; 60: 3899–903PubMed

57.

Schneider-Stock R, Boltze C, Lasota J, et al. High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol 2003; 21: 1688–97PubMedCrossRef

58.

Goldblum JR. DNA ploidy and proliferative index in gastrointestinal stromal tumors. Hum Pathol 1998; 29: 102PubMedCrossRef

59.

Cooper PN, Quirke P, Hardy GJ, et al. A flow cytometric, clinical, and histological study of stromal neoplasms of the gastrointestinal tract. Am J Surg Pathol 1992; 16: 163–70PubMedCrossRef

60.

Goldblum JR. Gastrointestinal stromal tumors: a review of characteristics morphologic, immunohistochemical and molecular genetic festures. Am J Clin Pathol 2002; 117 Suppl.: S49–61PubMed

61.

Gunawan B, von Heydebreck A, Sander B, et al. An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cyto-genetic evolution with prognostic implications. J Pathol 2007 Mar; 211(4): 463–70PubMedCrossRef

62.

Subramanian S, West RB, Corless CL, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene 2004; 23: 7780–90PubMedCrossRef

63.

Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 2002 Sep 15; 20(18): 3898–905PubMedCrossRef

64.

Hornick JL, Fletcher CDM. The role of KIT in the management of patients with gastrointestinal stromal tumors. Hum Pathol 2007; 38: 679–87PubMedCrossRef

65.

Heinrich MC, Corless CL, Duensing A, et al. PDGFRA Activating mutations in gastrointestinal stromal tumors. Science 2003; 299: 708–10PubMedCrossRef

66.

Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol 2006; 23: 91–102PubMedCrossRef

67.

Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib mesylate response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21: 4342–9PubMedCrossRef

68.

Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 2001; 61: 8118–21PubMed

69.

Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006; 24: 4764–74PubMedCrossRef

70.

Antonescu CR, Sommer G, Sarran L, et al. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 2003; 9: 3329–37PubMed

71.

Lasota J, Wozniak A, Sarlomo-Rikala M, et al. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors: a study of 200 cases. Am J Pathol 2000; 157: 1091–5PubMedCrossRef

72.

Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 2004; 28: 889–94PubMedCrossRef

73.

Debiec-Rychter M, Wasag B, Stul M, et al. Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 2004; 202: 430–8PubMedCrossRef

74.

Lasota J, Dansonka-Mieszkowska A, Sobin LH, et al. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004; 84: 874–83PubMedCrossRef

75.

Wozniak A, Rutkowski P, Sciot R, et al. Rectal gastrointestinal stromal tumors associated with a novel germline KIT mutation. Int J Cancer 2008 May 1; 122(9): 2160–4PubMedCrossRef

76.

Nishida T, Hirota S, Taniguchi M, et al. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 1998; 19: 323–4PubMedCrossRef

77.

Beghini A, Tibiletti MG, Roversi G, et al. Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer 2001; 92: 657–62PubMedCrossRef

78.

Maeyama H, Hidaka E, Ota H, et al. Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. Gastroenterology 2001; 120: 210–5PubMedCrossRef

79.

O’Brien P, Kapusta L, Dardick I, et al. Multiple familial gastrointestinal autonomic nerve tumors and small intestinal neuronal dysplasia. Am J Surg Pathol 1999; 23: 198–204PubMedCrossRef

80.

Isozaki K, Terris B, Belghiti J, et al. Germline-activating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol 2000; 157: 1581–5PubMedCrossRef

81.

Prakash S, Sarran L, Socci N, et al. Gastrointestinal stromal tumors in children and young adults. J Pediatr Hematol Oncol 2005; 27: 179–87PubMedCrossRef

82.

Maertens O, Prenen H, Debiec-Rychter M, et al. Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet 2006; 15: 1015–23PubMedCrossRef

83.

Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet 2002 Mar 1; 108(2): 132–9PubMedCrossRef

84.

Carney JA, Sheps SG, Go VL, et al. The triad of gastric leiomyosarcoma, functioning extra-adrenal paranganglioma and pulmonary chondroma. N Engl J Med 1977; 296: 1517–8PubMedCrossRef

85.

Carney JA. Gastric sarcoma, pulmonary chondroma and extra-adrenal paraganglioma (Carney’s triad): natural history, adrenocortical component and possible familial occurrence. Mayo Clin Proc 1999; 74: 543–52PubMedCrossRef

86.

Diment J, Tamborini E, Casali P, et al. Carney triad: case report and molecular analysis of gastric tumor. Human Pathol 2005; 36: 112–6CrossRef

87.

Beltran MA, Cruces KS, Barria C, et al. Multiple gastrointestinal stromal tumors of the ileum and neurofibromatosis type 1. J Gastroint Surg 2006; 10: 297–301CrossRef

88.

Haller F, Schulten H-J, Armburust T, et al. Multicentric sporadic gastrointestinal stromal tumors (GISTs) of the stomach with distinct clonal origin: differential diagnosis to familial and syndromal GIST variants and peritoneal metastases. Am J Surg Pathol 2007; 31: 933–7PubMedCrossRef

89.

Lasota J, Jasinski M, Sarlomo-Rikala M, et al. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999; 154: 53–60PubMedCrossRef

90.

Ernst SI, Hubbs AE, Przygodzki RM, et al. KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest 1998; 78: 1633–6PubMed

91.

Li SQ, O’Leary TJ, Sobin LH, et al. Analysis of KIT mutation and protein expression in fine needle aspirates of gastrointestinal stromal/ smooth muscle tumors. Acta Cytol 2000; 44: 981–6PubMedCrossRef

92.

Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 1999; 59: 4297–300PubMed

93.

Kim TW, Lee H, Kang YK, et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 2004 May 1; 10(9): 3076–81PubMedCrossRef

94.

Andersson J, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 2006; 130: 1573–81PubMedCrossRef

95.

Martin J, Poveda A, Llombart-Bosch A, et al. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol 2005; 23: 6190–8PubMedCrossRef

96.

Wardelmann E, Losen I, Hans V, et al. Deletion of Trp-557 and Lys-558 in the juxtamembranedomain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer 2003; 106: 887–95PubMedCrossRef

97.

Lasota J, Jerzak vel Dobosz A, Wasag B, et al. Presence of homozygous KIT exon 11 mutations is strongly associated with malignant clinical behavior in gastrointestinal stromal tumors. Lab Inv 2007 Oct; 87(10): 1029–41CrossRef

98.

Lasota J, Kopczynski J, Sarlomo-Rikala M, et al. KIT 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin. Hum Pathol 2003; 34: 1306–12PubMedCrossRef

99.

Hirota S, Nishida T, Izosaki K, et al. Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours. J Pathol 2001; 193: 505–10PubMedCrossRef

100.

Corless CL, McGreevey L, Haley A, et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 2002; 160: 1567–72PubMedCrossRef

101.

Agaimy A, Wunsch PH, Hofstaedter F, et al. Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol 2007; 31: 113–20PubMedCrossRef

102.

Kawanowa K, Sakuma Y, Sakurai S, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol 2006 Dec; 37(12): 1527–35PubMedCrossRef

103.

Pierie JP, Choudry U, Muzikansky A, et al. The effect of surgery and grade on outcome of gastrointestinal stromal tumors. Arch Surg 2001; 136: 383–9PubMedCrossRef

104.

Gutierrez JC, De Oliviera O, Perez EA, et al. Optimizing diagnosis, staging, and management of gastrointestinal stromal tumors. J Am Coll Surg 2007; 205(3): 479–91PubMedCrossRef

105.

Roberts PJ, Eisenberg B. Clinical presentation of gastrointestinal stromal tumors and treatement of operable disease. Eur J Cancer 2002; 38Suppl. 5: S37–8PubMedCrossRef

106.

Dematteo RP, Heinrich MC, El-Rifai WM, et al. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol 2002; 33(5): 466–77PubMedCrossRef

107.

Gold JS, van der Zwan SM, Gönen M, et al. Outcome of metastatic GIST in the era before tyrosine kinase inhibitors. Ann Surg Oncol 2007; 14: 134–42PubMedCrossRef

108.

Trent JC, Benjamin RS. New developments in gastrointestinal stromal tumor. Curr Opin Oncol 2006; 18: 386–95PubMedCrossRef

109.

Demetri GD. Targeting the molecular pathophysiology of gastrointestinal stromal tumors with imatinib: mechanisms, successes, and challenges to rational drug development. Hematol Oncol Clin North Am 2002; 16: 1115–24PubMedCrossRef

110.

Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001; 344(14): 1052–6PubMedCrossRef

111.

Buchdunger E, Ciotfi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000; 295(1): 13945

112.

Okuda K, Weisberg E, Gilliland DG, et al. ARG tyrosine kinase activity is inhibited by STI571. Blood 2001; 97(8): 2440–8PubMedCrossRef

113.

Mol CD, Dougan DR, Schneider TR, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chern 2004; 279(30): 31655–63CrossRef

114.

Dewar AL, Cambareri AC, Zannettino AC, et al. Macrophage colony stimulating factor receptor, c-fins, is a novel target ofimatinib. Blood 2005; 105(8): 3127–32PubMedCrossRef

115.

Dagher R, Cohen M, Williams G, et al. Approval summary: imatinib mesylate in the treamaent of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 2002; 8(10): 3034–8PubMed

116.

van Oosterom AT, Judson I, Verwiej J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: aphase I study. Lancet 2001; 358: 1421–3PubMedCrossRef

117.

van Oosterom AT, Judson IR, Verwiej J. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2002; 38,Suppl. 5: S83–7PubMedCrossRef

118.

Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347: 472–80PubMedCrossRef

119.

Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364: 1127–34PubMedCrossRef

120.

Blanke CD, Demetri GD, Von Mehren M, et al. Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate [abstract]. J Clin Oncol 2006; 24(18 Suppl.): 9528

121.

Rutkowski P, Nowecki ZI, Debiec-Rychter M, et al. Predictive factors for long term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol 2007 Sep; 133(9): 589–97PubMedCrossRef

122.

Choi H, Charnsangavej C, de Castro Faria S, et al. 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: 1619–28PubMed

123.

Blay JY, Le Cesne A, Ray-Coquard I, et al. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol 2007; 25: 1107–13PubMedCrossRef

124.

Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol 2005; 23: 5795–804PubMedCrossRef

125.

Hohenberger P, Reichardt P, Gebauer B, et al. Gastrointestinal stromal tumors (GIST): current concepts of surgical management. Dtsch Med Wochenschr 2004; 129: 1817–20PubMedCrossRef

126.

Rutkowski P, Nowecki ZI, Nyckowski P, et al. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol 2006; 4: 304–11CrossRef

127.

Bauer S, Hartmann JT, de Wit M, et al. Resection of residual disease in patients with metastatic gastrointestinal tumors responding to treatment with imatinib. Int J Cancer 2005 Nov 1; 117(2): 316–25PubMedCrossRef

128.

Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-tergeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg 2007; 245(3): 353–4CrossRef

129.

Andtbacka RHI, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 2007 Jan; 14(1): 14–21PubMedCrossRef

130.

Rutkowski P, Nowecki ZI, Nyckowski P. The updated outcomes of metastatic and/ or unresectable gastrointestinal stromal tumor (GIST) patients treated surgically after response to targeted therapy with imatinib (IM) [abstract no. 618]. 12th Annual Meeting of the Connective Tissue Oncology Society; 2006 Nov 2-4; Venice

131.

Eisenberg BL, Judson I. Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann Surg Oncol 2004; 11: 465–75PubMedCrossRef

132.

DeMatteo R, Owzar K, Maki R, et al. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001. J Clin Oncol 2007 ASCO Annual Meeting Proceedings 2007 Jun 20; 25 (18S Suppl.): 10079

133.

ClinicalTrials.gov. European Organization for Research and Treatment of Cancer (EORTC) 62024 trial. Imatinib mesylate or observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor: NCT00103168 [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00103168?term=eortc+62024&rank=l [Accessed 2008 May 5]

134.

Zalcberg JR, Verweij J, Casali PG, et al. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800mg after progression on 400 mg. Eur J Cancer 2005; 41(12): 1751–7PubMedCrossRef

135.

Abrams TJ, Lee LB, Murray LJ, et al. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2003; 2: 471–8PubMed

136.

O’Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003; 101: 3597–605PubMedCrossRef

137.

Murray LJ, Abrams TJ, Long KR, et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 2003; 20: 757–66PubMedCrossRef

138.

Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003; 9: 327–37PubMed

139.

Kim DW, Jo YS, Jung HS, et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/ papillary thyroid cancer kinases. J Clin Endocrinol Metab 2006; 91: 4070–6PubMedCrossRef

140.

Maki R, Fletcher J, Heinrich M, et al. Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST) [abstract no. 9011]. J Clin Oncol 2005; 23 (16 Suppl.)

141.

Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329–38PubMedCrossRef

142.

Reichardt P, Kang YK, Ruka W, et al. Subpopulation analyses in a worldwide treatment-use trial of sunitinib (SU) in GIST patients (pts) with resistance or intolerance to prior imatinib (IM) therapy [abstract no. 10022]. J Clin Oncol 2007; 25(18 Suppl.): 550S

143.

Hopkins TG, Marples M, Stark D. Sunitinib in the management of gastrointestinal stromal tumours (GISTs). Eur J Surg Oncol. Epub 2007 Dec 12

144.

George S, Blay JY, Casali PG, et al. Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST [abstract no. 10015]. J Clin Oncol 2007; 25(18 Suppl.): 548S

145.

Heinrich MC, Shoemaker JS, Corless CL, et al. Correlation of target kinase genotype with clinical activity of imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT (KIT+) [abstract no. 7]. J Clin Oncol 2005; 23(16 Suppl.): 7

146.

Debiec-Rychter M, Dumez H, Judson I, et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004; 40(5): 689–95PubMedCrossRef

147.

Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006; 42: 1093–103PubMedCrossRef

148.

Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005; 23: 5357–64PubMedCrossRef

149.

Van Glabbeke MM, Owzar K, Rankin C, et al. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): a meta-analysis based on 1,640 patients (pts) [abstract no. 10004]. J Clin Oncol 2007; 25(18 Suppl.): 546S

150.

Duensing A, Medeiros F, McConarty B, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumours (GISTs). Oncogene 2004; 23: 3999–4006PubMedCrossRef

151.

Fletcher JA, Corless CL, Dimitrijevic S, et al. Mechanisms of resistance to imatinib mesylate (IM) in advanced gastrointestinal stromal tumor (GIST) [abstract no. 3275]. Proc Am Soc Clin Oncol 2003; 22: 815

152.

Debiec-Rychter M, Cools J, Dumez H, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 2005; 128: 270–9PubMedCrossRef

153.

Antonescu CR, Besmer P, Guo T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 2005; 11: 4182–90PubMedCrossRef

154.

Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 2006; 12: 1743–9PubMedCrossRef

155.

Wardelmann E, Thomas N, Merkelabch-Bruse S, et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol 2005; 6: 249–51PubMedCrossRef

156.

Chen LL, Trent JC, Wu EF, et al. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 2004; 64: 5913–9PubMedCrossRef

157.

Roberts KG, Odell AF, Byrnes EM, et al. Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Mol Cancer Ther 2007; 6(3): 1159–66PubMedCrossRef

158.

Tamborini E, Bonadiman L, Greco A, et al. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 2004 Jul; 127(1): 294–9PubMedCrossRef

159.

Wakai T, Kanda T, Hirota S, et al. Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Br J Cancer 2004; 90: 2059–61PubMed

160.

Utsunomiya T, Okamoto M, Yano S, et al. Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case. Surg Today 2008; 38: 65–7PubMedCrossRef

161.

Prenen H, Cools J, Mentens N, et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 2006; 12: 2622–7PubMedCrossRef

162.

Guo T, Agaram NP, Wong GC, et al. Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumors. Clin Cancer Res 2007; 13: 4874–81PubMedCrossRef

163.

Schittenhelm MM, Shiraga S, Schroeder A, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 2006; 66: 473–81PubMedCrossRef

164.

Heinrich MC, Maki R, Corless CL, et al. Sunitinib (SU) response in imatinibresistant (IM-R) GIST correlates with KIT and PDGFRA mutation status [abstract no. 9502]. Proc Am Soc Clin Oncol 2006 Jun 20; 24(18 Suppl.): 520S

165.

Demetri GD, Benjamin RS, Blanke CD, et al. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST): update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 2007; 5: S1–2PubMed

Titel: Gastrointestinal Stromal Tumors
Key to Diagnosis and Choice of Therapy
verfasst von: Dr Piotr Rutkowski
Maria Debiec-Rychter
Wlodzimierz Ruka
Publikationsdatum: 01.05.2008
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 3/2008
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/BF03256278

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Gastrointestinal Stromal Tumors

Key to Diagnosis and Choice of Therapy

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2008

Lucica® MI Urinary Myoinositol Kit

Biomarkers for Osteoporosis Management

Cerebral Small Vessel Disease

Molecular Medicine TriConference 2008

The Effects of Immunosuppression on Regulatory CD4+CD25+ T Cells

From the World Literature

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Update Innere Medizin