The role of KIT in the management of patients with gastrointestinal stromal tumors

Human Pathology

Volumn 38, Issue 5, 2007, Pages 679-687

  Hornick, Jason L ^a,b   Fletcher, Christopher D M ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Gastrointestinal stromal tumor; GIST; Imatinib; KIT; Sarcoma

Indexed keywords

IMATINIB; PLATELET DERIVED GROWTH FACTOR A; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; STEM CELL FACTOR RECEPTOR; SUNITINIB;

CONTROLLED STUDY; EXON; GASTROINTESTINAL STROMAL TUMOR; GENE ACTIVATION; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN EXPRESSION; REVIEW; SURVIVAL TIME;

ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL STROMAL TUMORS; HUMANS; INDOLES; MUTATION; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; PYRIMIDINES; PYRROLES; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA;

EID: 34147103980     PISSN: 00468177     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.humpath.2007.03.001     Document Type: Review

References (93)

1. Hurlimann J., and Gardiol D. Gastrointestinal stromal tumours: an immunohistochemical study of 165 cases. Histopathology 19 (1991) 311-320
2. Newman P.L., Wadden C., and Fletcher C.D. Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathological features. J Pathol 164 (1991) 107-117
3. Pike A.M., Lloyd R.V., and Appelman H.D. Cell markers in gastrointestinal stromal tumors. Hum Pathol 19 (1988) 830-834
4. Ma C.K., Amin M.B., Kintanar E., et al. Immunohistologic characterization of gastrointestinal stromal tumors: a study of 82 cases compared with 11 cases of leiomyomas. Mod Pathol 6 (1993) 139-144
5. Saul S.H., Rast M.L., and Brooks J.J. The immunohistochemistry of gastrointestinal stromal tumors. Evidence supporting an origin from smooth muscle. Am J Surg Pathol 11 (1987) 464-473
6. Hirota S., Isozaki K., Moriyama Y., et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279 (1998) 577-580
7. Sarlomo-Rikala M., Kovatich A.J., Barusevicius A., et al. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 11 (1998) 728-734
8. Kindblom L.G., Remotti H.E., Aldenborg F., et al. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152 (1998) 1259-1269
9. Druker B.J., Tamura S., Buchdunger E., et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2 (1996) 561-566
10. Druker B.J., Talpaz M., Resta D.J., et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344 (2001) 1031-1037
11. Heinrich M.C., Griffith D.J., Druker B.J., et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96 (2000) 925-932
12. Tuveson D.A., Willis N.A., Jacks T., et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20 (2001) 5054-5058
13. van Oosterom A.T., Judson I., Verweij J., et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358 (2001) 1421-1423
14. Demetri G.D., von Mehren M., Blanke C.D., et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347 (2002) 472-480
15. Verweij J., Casali P.G., Zalcberg J., et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364 (2004) 1127-1134
16. Dematteo R.P., Heinrich M.C., El-Rifai W.M., et al. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol 33 (2002) 466-477
17. Huizinga J.D., Thuneberg L., Kluppel M., et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373 (1995) 347-349
18. Maeda H., Yamagata A., Nishikawa S., et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116 (1992) 369-375
19. Corless C.L., McGreevey L., Haley A., et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 160 (2002) 1567-1572
20. Heinrich M.C., Corless C.L., Demetri G.D., et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21 (2003) 4342-4349
21. Rubin B.P., Singer S., Tsao C., et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61 (2001) 8118-8121
22. Lux M.L., Rubin B.P., Biase T.L., et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156 (2000) 791-795
23. Debiec-Rychter M., Sciot R., LeCesne A., et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42 (2006) 1093-1103
24. Heinrich M.C., Corless C.L., Duensing A., et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299 (2003) 708-710
25. 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 125 (2003) 660-667
26. 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 40 (2004) 689-695
27. Antonescu C.R., Besmer P., Guo T., et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11 (2005) 4182-4190
28. 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 128 (2005) 270-279
29. 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 90 (2004) 2059-2061
30. 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 127 (2004) 294-299
31. Chen L.L., Trent J.C., Wu E.F., et al. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 64 (2004) 5913-5919
32. Wardelmann E., Thomas N., Merkelbach-Bruse S., et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol 6 (2005) 249-251
33. 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 12 (2006) 1743-1749
34. Heinrich M.C., Corless C.L., Blanke C.D., et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24 (2006) 4764-4774
35. Ma Y., Zeng S., Metcalfe D.D., et al. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood 99 (2002) 1741-1744
36. Heinrich M.C., Rubin B.P., Longley B.J., et al. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 33 (2002) 484-495
37. Corless C.L., Schroeder A., Griffith D., et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23 (2005) 5357-5364
38. Demetri G.D., vanOosterom A.T., Garrett C.R., et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368 (2006) 1329-1338
39. DeMatteo R.P., Lewis J.J., Leung D., et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231 (2000) 51-58
40. Miettinen M., Sobin L.H., and 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 29 (2005) 52-68
41. Miettinen M., Makhlouf H., Sobin L.H., 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 30 (2006) 477-489
42. Reith J.D., Goldblum J.R., Lyles R.H., et al. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 13 (2000) 577-585
43. Miettinen M., Monihan J.M., Sarlomo-Rikala M., et al. Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol 23 (1999) 1109-1118
44. Yamamoto H., Oda Y., Kawaguchi K., et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol 28 (2004) 479-488
45. Fletcher C.D., Berman J.J., Corless C., et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33 (2002) 459-465
46. Miettinen M., and Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 23 (2006) 70-83
47. Andtbacka R.H., Ng C.S., Scaife C.L., et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 14 (2007) 14-24
48. Bumming P., Andersson J., Meis-Kindblom J.M., et al. Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer 89 (2003) 460-464
49. Raut C.P., Posner M., Desai J., et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol 24 (2006) 2325-2331
50. Hornick J.L., and Fletcher C.D. Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol 117 (2002) 188-193
51. Miettinen M.M., Sarlomo-Rikala M., Kovatich A.J., et al. Calponin and h-caldesmon in soft tissue tumors: consistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicates traits of smooth muscle differentiation. Mod Pathol 12 (1999) 756-762
52. Miettinen M., Sarlomo-Rikala M., Sobin L.H., 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 24 (2000) 211-222
53. Miettinen M., Sarlomo-Rikala M., and Sobin L.H. Mesenchymal tumors of muscularis mucosae of colon and rectum are benign leiomyomas that should be separated from gastrointestinal stromal tumors-a clinicopathologic and immunohistochemical study of eighty-eight cases. Mod Pathol 14 (2001) 950-956
54. Pauls K., Merkelbach-Bruse S., Thal D., et al. PDGFRalpha- and c-kit-mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features. Histopathology 46 (2005) 166-175
55. Medeiros F., Corless C.L., Duensing A., et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 28 (2004) 889-894
56. Debiec-Rychter M., Wasag B., Stul M., et al. Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 202 (2004) 430-438
57. Weisberg E., Wright R.D., Jiang J., et al. Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity. Gastroenterology 131 (2006) 1734-1742
58. Yantiss R.K., Spiro I.J., Compton C.C., et al. Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis. Am J Surg Pathol 24 (2000) 947-957
59. Miettinen M., Sobin L.H., and Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 13 (2000) 1134-1142
60. Lucas D.R., al-Abbadi M., Tabaczka P., et al. c-Kit expression in desmoid fibromatosis. Comparative immunohistochemical evaluation of two commercial antibodies. Am J Clin Pathol 119 (2003) 339-345
61. Heinrich M.C., McArthur G.A., Demetri G.D., et al. Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). J Clin Oncol 24 (2006) 1195-1203
62. McArthur G.A., Demetri G.D., van Oosterom A., et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol 23 (2005) 866-873
63. Simon M.P., Pedeutour F., Sirvent N., et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 15 (1997) 95-98
64. Shimizu A., O'Brien K.P., Sjoblom T., et al. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 59 (1999) 3719-3723
65. Kemmer K., Corless C.L., Fletcher J.A., et al. KIT mutations are common in testicular seminomas. Am J Pathol 164 (2004) 305-313
66. Tian Q., Frierson Jr. H.F., Krystal G.W., et al. Activating c-kit gene mutations in human germ cell tumors. Am J Pathol 154 (1999) 1643-1647
67. Longley B.J., Tyrrell L., Lu S.Z., et al. Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. Nat Genet 12 (1996) 312-314
68. Schittenhelm M.M., 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 66 (2006) 473-481
69. Shah N.P., Lee F.Y., Luo R., et al. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood 108 (2006) 286-291
70. Gleixner K.V., Mayerhofer M., Aichberger K.J., et al. PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects. Blood 107 (2006) 752-759
71. Gotlib J., Berube C., Growney J.D., et al. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood 106 (2005) 2865-2870
72. Corbin A.S., Griswold I.J., La Rosee P., et al. Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970. Blood 104 (2004) 3754-3757
73. Miettinen M., Sarlomo-Rikala M., and Lasota J. KIT expression in angiosarcomas and fetal endothelial cells: lack of mutations of exon 11 and exon 17 of C-kit. Mod Pathol 13 (2000) 536-541
74. Dy G.K., Miller A.A., Mandrekar S.J., et al. A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Ann Oncol 16 (2005) 1811-1816
75. Krug L.M., Crapanzano J.P., Azzoli C.G., et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer 103 (2005) 2128-2131
76. 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 34 (2003) 1306-1312
77. Ernst S.I., Hubbs A.E., Przygodzki R.M., et al. KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest 78 (1998) 1633-1636
78. 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 154 (1999) 53-60
79. Agaimy A., Wunsch P.H., 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 31 (2007) 113-120
80. Nishida T., Hirota S., Taniguchi M., et al. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 19 (1998) 323-324
81. Hirota S., Nishida T., Isozaki K., et al. Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene. Gastroenterology 122 (2002) 1493-1499
82. 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 157 (2000) 1581-1585
83. Li F.P., Fletcher J.A., Heinrich M.C., et al. Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 23 (2005) 2735-2743
84. Hirota S., Okazaki T., Kitamura Y., et al. Cause of familial and multiple gastrointestinal autonomic nerve tumors with hyperplasia of interstitial cells of Cajal is germline mutation of the c-kit gene. Am J Surg Pathol 24 (2000) 326-327
85. O'Brien P., Kapusta L., Dardick I., et al. Multiple familial gastrointestinal autonomic nerve tumors and small intestinal neuronal dysplasia. Am J Surg Pathol 23 (1999) 198-204
86. 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 120 (2001) 210-215
87. Sommer G., Agosti V., Ehlers I., et al. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci U S A 100 (2003) 6706-6711
88. Rubin B.P., Antonescu C.R., Scott-Browne J.P., et al. A knock-in mouse model of gastrointestinal stromal tumor harboring kit K641E. Cancer Res 65 (2005) 6631-6639
89. Wardelmann E., Hrychyk A., Merkelbach-Bruse S., et al. Association of platelet-derived growth factor receptor alpha mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. J Mol Diagn 6 (2004) 197-204
90. Lasota J., Dansonka-Mieszkowska A., Sobin L.H., et al. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 84 (2004) 874-883
91. Lasota J., Stachura J., and Miettinen M. GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology. Lab Invest 86 (2006) 94-100
92. Heinrich M.C., Maki R.G., Corless C.L., et al. Sunitinib (SU) response in imatinib-resistant (IM-R) GIST correlates with KIT and PDGFRA mutation status. J Clin Oncol 24 Suppl (2006) 9502
93. Bauer S., Yu L.K., Demetri G.D., et al. Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res 66 (2006) 9153-9161