Gastrointestinal stromal tumors

Virchows Archiv

Volumn 456, Issue 2, 2010, Pages 111-127

  Liegl Atzwanger, Bernadette ^a,b   Fletcher, Jonathan A ^a   Fletcher, Christopher D M ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Gastrointestinalstromal tumor; GIST; Imatinib; KIT; PDGFRA; Resistance; Sunitinib; Tyrosine kinase inhibitors

Indexed keywords

BIOLOGICAL MARKER; BORTEZOMIB; CYCLIN DEPENDENT KINASE INHIBITOR 1B; CYCLIN DEPENDENT KINASE INHIBITOR 2A; HISTONE DEACETYLASE INHIBITOR; IMATINIB; NILOTINIB; PLACEBO; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; STEM CELL FACTOR RECEPTOR; SUNITINIB; PROTEIN TYROSINE KINASE; TUMOR MARKER;

CANCER EPIDEMIOLOGY; CANCER MORPHOLOGY; CARNEY COMPLEX; CHILDHOOD CANCER; CLINICAL FEATURE; CLINICAL TRIAL; CYTOGENETICS; DIAGNOSTIC ACCURACY; DIAGNOSTIC VALUE; DIFFERENTIAL DIAGNOSIS; DISEASE ASSOCIATION; DISEASE MARKER; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; FAMILIAL CANCER; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; GENETIC ANALYSIS; HUMAN; IMMUNOHISTOCHEMISTRY; MOLECULAR DYNAMICS; NEUROFIBROMATOSIS; NONHUMAN; ONCOGENE C KIT; PATHOGENESIS; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; RECOMMENDED DRUG DOSE; REVIEW; RISK ASSESSMENT; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; TUMOR CLASSIFICATION; TUMOR GROWTH; TUMOR REGRESSION; TUMOR RESISTANCE; DRUG ANTAGONISM; DRUG RESISTANCE; GENETICS; METABOLISM;

DRUG RESISTANCE, NEOPLASM; GASTROINTESTINAL STROMAL TUMORS; HUMANS; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS C-KIT; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA; TUMOR MARKERS, BIOLOGICAL;

EID: 77950345223     PISSN: 09456317     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00428-010-0891-y     Document Type: Review

References (165)

1. Demetri GD, Benjamin RS, Blanke CD et al (2007) NCCN Task force report: management of patients with gastrointestinal stromal tumor (GIST)-update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 5(Suppl 2):S1-S29
2. Edmonson JH, Marks RS, Buckner JC et al (2002) Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Investig 20(5-6):605-612
3. Fletcher CD, Berman JJ, Corless C et al (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Human Pathol 33:459-465 (Pubitemid 34747864)
4. Mazur MT, Clark HB (1983) Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 7(6):507-519
5. Miettinen M, Virolainen M, Maarit Sarlomo R (1995) Gastrointestinal stromal tumors-value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas. Am J Surg Pathol 19(2):207-216
6. Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279(5350):577-580 (Pubitemid 28067289)
7. Huizinga JD, Thuneberg L, Kluppel M et al (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373(6512):347-349
8. Kindblom L, Ramotti H, Aldenborg F et al (1998) Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259-1269 (Pubitemid 28221878)
9. Robinson TL, Sircar K, Hewlett BR et al (2000) Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal. Am J Pathol 156(4):1157-1163 (Pubitemid 30659992)
10. Janeway KA, Liegl B, Harlow A et al (2007) Pediatric KIT wildtype and platelet-derived growth factor receptor alpha wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 67(19):9084-9088 (Pubitemid 47535893)
11. Isozaki K, Hirota S, Nakama A et al (1995) Disturbed intestinal movement, bile reflux to the stomach, and deficiency of c-kitexpressing cells in Ws/Ws mutant rats. Gastroenterology 109 (2):456-464
12. Heinrich MC, Corless CL, Duensing A et al (2003) PDGFRAactivating mutations in gastrointestinal stromal tumors. Science 299(5607):708-710 (Pubitemid 36159485)
13. Heinrich MC, Corless CL, Demetri GD et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342-4349 (Pubitemid 46621810)
14. Corless CL, Fletcher JA, Heinrich MC (2004) Biology of gastrointestinal stromal tumors. J Clin Oncol 22(18):3813-3825
15. Hornick JL, Fletcher CD (2002) Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol 117(2):188-193
16. Hornick JL, Fletcher CD (2007) The role of KIT in the management of patients with gastrointestinal stromal tumors. Human Pathol 38(5):679-687 (Pubitemid 46560810)
17. Stenman G, Eriksson A, Claesson-Welsh L (1989) Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene. Genes Chromos Cancer 1(2):155-158 (Pubitemid 20094560)
18. Hubbard SR (2004) Juxtamembrane autoinhibition in receptor tyrosine kinases. Nat Rev Mol Cell Biol 5(6):464-471
19. Pawson T (2002) Regulation and targets of receptor tyrosine kinases. Eur J Cancer 38(Suppl 5):S3-S10
20. Blume-Jensen P, Claesson-Welsh L, Siegbahn A et al (1991) Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis. Embo J 10(13):4121-4128 (Pubitemid 21905443)
21. O'Farrell AM, Abrams TJ, Yuen HA et al (2003) SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101(9):3597-3605
22. Casteran N, De Sepulveda P, Beslu N et al (2003) Signal transduction by several KIT juxtamembrane domain mutations. Oncogene 22(30):4710-4722 (Pubitemid 36976446)
23. Duensing A, Medeiros F, McConarty B et al (2004) Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene 23(22):3999-4006 (Pubitemid 38747928)
24. Kitayama H, Kanakura Y, Furitsu T et al (1995) Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factordependent hematopoietic cell lines. Blood 85(3):790-798
25. Rossi F, Ehlers I, Agosti Vet al (2006) Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor. Proc Natl Acad Sci U S A 103(34):12843-12848 (Pubitemid 44298649)
26. Lev S, Blechman J, Nishikawa S et al (1993) Interspecies molecular chimeras of kit help define the binding site of the stem cell factor. Mol Cell Biol 13(4):2224-2234 (Pubitemid 23097701)
27. Maeda H, Yamagata A, Nishikawa S et al (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116(2):369-375
28. Duensing A, Joseph NE, Medeiros F et al (2004) Protein kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res 64 (15):5127-5131 (Pubitemid 39006529)
29. Rubin BP, Singer S, Tsao C et al (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61(22):8118-8121 (Pubitemid 33091601)
30. Corless CL, Heinrich MC (2008) Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 3:557-586
31. Lasota J, Dansonka-Mieszkowska A, Stachura T et al (2003) Gastrointestinal stromal tumors with internal tandem duplications in 3 end of KIT juxtamembrane domain occur predominantly in stomach and generally seem to have a favorable course. Mod Path 16(12):1257-1264 (Pubitemid 38018608)
32. Lasota J, Miettinen M (2008) Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 53(3):245-266
33. Wardelmann E, Losen I, Hans Vet al (2003) 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 106(6):887-895 (Pubitemid 37071667)
34. Antonescu CR, Sommer G, Sarran L et al (2003) 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 9 (9):3329-3337 (Pubitemid 37082727)
35. Miettinen M, Makhlouf H, Sobin LH et al (2006) 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(4):477-489 (Pubitemid 43740149)
36. Heinrich MC, Owzar K, Corless CL et al (2008) Correlation of kinase genotype and clinical outcome in the North American intergroup phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol 26(33):5360-5367
37. Lasota J, Corless CL, Heinrich MC et al (2008) Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases. Mod Path 21(4):476-484 (Pubitemid 351441037)
38. Debiec-Rychter M, Wasag B, Stul M et al (2004) Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 202(4):430-438 (Pubitemid 38456161)
39. Medeiros F, Corless CL, Duensing A et al (2004) KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 28(7):889-894 (Pubitemid 38856844)
40. Wardelmann E, Hrychyk A, Merkelbach-Bruse S et al (2004) 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 (3):197-204 (Pubitemid 39136646)
41. Lasota J, Dansonka-Mieszkowska A, Sobin LH et al (2004) A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 84 (7):874-883 (Pubitemid 38833247)
42. Lasota J, Stachura J, Miettinen M (2006) GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology. Lab Invest 86(1):94-100 (Pubitemid 43250972)
43. Debiec-Rychter M, Sciot R, Le Cesne A et al (2006) KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42(8):1093-1103 (Pubitemid 44275331)
44. Corless CL, Schroeder A, Griffith D et al (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23(23):5357-5364 (Pubitemid 46206989)
45. Hirota S, Ohashi A, Nishida T et al (2003) Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 125(3):660-667 (Pubitemid 37070684)
46. Mendel DB, Laird AD, Xin X et al (2003) 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 9(1):327-337
47. Ma Y, Cunningham ME, Wang X et al (1999) Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region. J Biol Chem 274(19):13399-13402 (Pubitemid 129518551)
48. Agaimy A, Terracciano LM, Dirnhofer S et al (2009) V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol 62(7):613-616
49. Agaram NP, Wong GC, Guo T et al (2008) Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromos Cancer 47(10):853-859
50. Hostein I, Faur N, Primois C et al (2010) BRAF mutation status in gastrointestinal stromal tumors. Am J Clin Pathol 133(1):141-148
51. Agaimy A, Wunsch PH, Dirnhofer S et al (2008) Microscopic gastrointestinal stromal tumors in esophageal and intestinal surgical resection specimens: a clinicopathologic, immunohistochemical, and molecular study of 19 lesions. Am J Surg Pathol 32(10):1553-1559
52. Kawanowa K, Sakuma Y, Sakurai S et al (2006) High incidence of microscopic gastrointestinal stromal tumors in the stomach. Human Pathol 37(12):1527-1535 (Pubitemid 44792229)
53. Corless CL, McGreevey L, Haley A et al (2002) KIT mutations are common in incidental gastrointestinal stromal zumors one centimeter or less in size. Am J Pathol 160(5):1567-1572 (Pubitemid 34525636)
54. Debiec-Rychter M, Lasota J, Sarlomo-Rikala M et al (2001) Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation with c-KIT gene mutation. Cancer Genet Cytogenet 128(1):24-30 (Pubitemid 32655477)
55. Fukasawa T, Chong JM, Sakurai S et al (2000) 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 91(12):1241-1249 (Pubitemid 32042358)
56. El-Rifai W, Sarlomo-Rikala M, Miettinen M et al (1996) DNA copy number losses in chromosome 14: an early change in gastrointestinal stromal tumors. Cancer Res 56(14):3230-3233 (Pubitemid 26242968)
57. Bergmann FGB, Hermanns B et al (1998) Cytogenetic and morphologic characteristics of gastrointestinal stromal tumors. Recurrent rearrangement of chromosome 1 and losses of chromosomes 14 and 22 as common anomalies. Verh Dtsch Ges Pathol 82:275-278
58. Kim NG, Kim JJ, Ahn JY et al (2000) Putative chromosomal deletions on 9P, 9Q and 22Q occur preferentially in malignant gastrointestinal stromal tumors. Int J Cancer 85(5):633-638
59. Lasota J, vel Dobosz AJ, Wasag B et al (2007) Presence of homozygous KIT exon 11 mutations is strongly associated with malignant clinical behavior in gastrointestinal stromal tumors. Lab Invest 87(10):1029-1041 (Pubitemid 47429185)
60. El-Rifai W, Sarlomo-Rikala M, Andersson LC et al (2000) Highresolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci. Genes Chromos Cancer 27(4):387-391 (Pubitemid 30127627)
61. Schurr P, Wolter S, Kaifi J et al (2006) Microsatellite DNA alterations of gastrointestinal stromal tumors are predictive for outcome. Clin Cancer Res 12(17):5151-5157 (Pubitemid 44453343)
62. Belinsky MG, Skorobogatko YV, Rink L et al (2009) High density DNA array analysis reveals distinct genomic profiles in a subset of gastrointestinal stromal tumors. Genes Chromos Cancer 48(10):886-896
63. Nilsson B, Bumming 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 (4):821-829 (Pubitemid 40216412)
64. Goettsch WG, Bos SD, Breekveldt-Postma N et al (2005) Incidence of gastrointestinal stromal tumours is underestimated: results of a nationwide study. Eur J Cancer 41(18):2868-2872 (Pubitemid 41713125)
65. Tryggvason G, Gislason HG, Magnusson MK et al (2005) Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 117(2):289-293 (Pubitemid 41377450)
66. Agaimy A, Wunsch 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(1):113-120 (Pubitemid 46036910)
67. Abraham SC, Krasinskas AM, Hofstetter WL et al (2007) "Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. Am J Surg Pathol 31(11):1629-1635
68. Miettinen M, Sobin LH, Lasota J (2005) Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1,765 cases with long-term follow-up. Am J Surg Pathol 29(1):52-68 (Pubitemid 40023952)
69. Prakash S, Sarran L, Socci N et al (2005) Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol 27(4):179-187 (Pubitemid 40604837)
70. Miettinen M, Lasota J, Sobin LH (2005) Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol 29(10):1373-1381 (Pubitemid 41368774)
71. Beghini A, Tibiletti MG, Roversi G et al (2001) Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer 92(3):657-662 (Pubitemid 32735203)
72. Isozaki K, Terris B, Belghiti J et al (2000) Germline-activating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol 157(5):1581-1585
73. Kang DY, Park CK, Choi JS et al (2007) Multiple gastrointestinal stromal tumors: clinicopathologic and genetic analysis of 12 patients. Am J Surg Pathol 31(2):224-232 (Pubitemid 46175023)
74. Maeyama H, Hidaka E, Ota H et al (2001) Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. Gastroenterology 120(1):210-215
75. Nishida T, Hirota S, Taniguchi M et al (1998) Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 19(4):323-324 (Pubitemid 28357901)
76. O'Riain C, Corless CL, Heinrich MC et al (2005) Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features. Am J Surg Pathol 29(12):1680-1683
77. Kleinbaum EP, Lazar AJ, Tamborini E et al (2008) Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. Int J Cancer 122 (3):711-718
78. 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(1):79-88
79. Li FP, Fletcher JA, Heinrich MC et al (2005) Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 23(12):2735-2743
80. Andersson J, Sihto H, Meis-Kindblom JM et al (2005) NF1- associated gastrointestinal stromal tumors have unique clinical, phenotypic, and genotypic characteristics. Am J Surg Pathol 29 (9):1170-1176
81. Maertens O, Prenen H, Debiec-Rychter M et al (2006) Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet 15(6):1015-1023
82. Miettinen M, Fetsch JF, Sobin LH et al (2006) Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30(1):90-96
83. Carney JA (1999) Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc 74(6):543-552
84. Carney JA, Stratakis CA (2002) Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet 108(2):132-139
85. DeMatteo RP, Lewis JJ, Leung D et al (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231(1):51-58
86. Miettinen M, Monihan JM, Sarlomo-Rikala M et al (1999) 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 (9):1109-1118
87. Reith JD, Goldblum JR, Lyles RH et al (2000) Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Path 13 (5):577-585
88. Agaimy A, Markl B, Arnholdt H et al (2009) Multiple sporadic gastrointestinal stromal tumours arising at different gastrointestinal sites: pattern of involvement of the muscularis propria as a clue to independent primary GISTs. Virchows Arch 455(2):101-108
89. Verma P, Corless C, Medeiros F et al (2005) Pleomorphic gastrointestinal stromal tumors: diagnostic and therapeutic implications. Mod Pathol 18(suppl 1):121A, abstract
90. Antonescu CR, Hornick JL, Nielsen GP et al (2007) Dedifferentiation in gastrointestinal stromal tumor (GIST) to an anaplastic KIT-negative phenotype-a diagnostic pitfall. Mod Pathol 20 (suppl 2):11A, abstract
91. Pauwels P, Debiec-Rychter M, Stul M et al (2005) Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall. Histopathology 47(1):41-47
92. Liegl B, Hornick JL, Antonescu C et al (2009) Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after tyrosine kinase inhibitor therapy: a novel form of tumor progression. Am J Surg Pathol 33(2):218-226
93. Janeway KA, Albritton KH, Van Den Abbeele AD et al (2009) Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer 52(7):767-771
94. Heinrich MC, Maki RG, Corless CL et al (2008) Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 26(33):5352-5359
95. Zhang L, Smyrk TC, Young WF Jr et al (2010) Gastric stromal tumors in Carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases. Am J Surg Pathol 34(1):53-64
96. Sarlomo-Rikala M, Kovatich A, Barusevicius A et al. (1998). CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Path (11):728-734
97. Miettinen M, Lasota J (2005) KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13(3):205-220
98. Orosz Z, Tornoczky T, Sapi Z (2005) Gastrointestinal stromal tumors: a clinicopathologic and immunohistochemical study of 136 cases. Pathol Oncol Res 11(1):11-21
99. Liegl B, Hornick JL, Corless C et al (2009) Monoclonal antibody DOG 1.1 shows higher sensitivity than KIT in the diagnosis of Gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol 33(3):437-446
100. West RB, Corless CL, Chen X et al (2004) The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 165(1):107-113
101. Espinosa I, Lee CH, Kim MK et al (2008) A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 32(2):210-218
102. Miettinen M, Wang ZF, Lasota J (2009) DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1,840 cases. Am J Surg Pathol 33(9):1401-1408
103. Blay P, Astudillo A, Buesa JM et al (2004) Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias. Clin Cancer Res 10(12 Pt 1):4089-4095
104. Lee HE, Kim MA, Lee HS et al (2008) Characteristics of KITnegative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining. J Clin Pathol 61(6):722-729
105. Rossi G, Valli R, Bertolini F et al (2005) PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract. Histopathology 46(5):522-531
106. Peterson MR, Piao Z, Weidner N et al (2006) Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors: immunohistochemical and mutational analyses. Appl Immunohistochem Mol Morphol 14(4):390-396
107. Zheng S, Chen LR, Wang HJ et al (2007) Analysis of mutation and expression of c-kit and PDGFR-alpha gene in gastrointestinal stromal tumor. Hepatogastroenterology 54(80):2285-2290
108. Miselli F, Millefanti C, Conca E et al (2008) PDGFRA immunostaining can help in the diagnosis of gastrointestinal stromal tumors. Am J Surg Pathol 32(5):738-743
109. Yang XH, Wu QL, Yu XB et al (2008) Nestin expression in different tumours and its relevance to malignant grade. J Clin Pathol 61(4):467-473
110. Parkkila S, Lasota J, Fletcher J A et al. (2010) Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors. Mod Pathol (in press)
111. Price ND, Trent J, El-Naggar AK et al (2007) Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas. Proc Natl Acad Sci U S A 104 (9):3414-3419
112. Sarlomo-Rikala M, Miettinen M (1995) Gastric schwannoma-a clinicopathological analysis of six cases. Histopathology 27 (4):355-360
113. Carlson JW, Fletcher CD (2007) Immunohistochemistry for betacatenin in the differential diagnosis of spindle cell lesions: analysis of a series and review of the literature. Histopathology 51(4):509-514
114. Montgomery E, Torbenson MS, Kaushal M et al (2002) Betacatenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 26(10):1296-1301
115. Lucas DR, al-Abbadi M, Tabaczka P et al (2003) C-Kit expression in desmoid fibromatosis. Comparative immunohistochemical evaluation of two commercial antibodies. Am J Clin Pathol 119(3):339-345
116. CessnaMH, Zhou H, SangerWG et al (2002) Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Path 15(9):931-938
117. Lasota J, Wang ZF, Sobin LH et al (2009) Gain-of-function PDGFRA mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases. Mod Path 22(8):1049-1056
118. Schildhaus HU, Cavlar T, Binot E et al (2008) Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. J Pathol 216(2):176-182
119. Antonescu CR, Nafa K, Segal NH et al (2006) EWS-CREB1: a recurrent variant fusion in clear cell sarcoma-association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 12(18):5356-5362
120. Lyle PL, Amato CM, Fitzpatrick JE et al (2008) Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg Pathol 32(6):858-866
121. Fletcher CD, Berman JJ, Corless C et al (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol 10(2):81-89 (Pubitemid 34655094)
122. Miettinen M, Lasota J (2006) Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 23(2):70-83
123. Joensuu H (2008) Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Human Pathol 39(10):1411-1419
124. Woodall CE 3rd, Brock GN, Fan J et al (2009) An evaluation of 2,537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg 144(7):670-678
125. Gold JS, Gonen M, Gutierrez A et al (2009) Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncol 10(11):1045-1052
126. Perrone F, Tamborini E, Dagrada GP et al (2005) 9p21 locus analysis in high-risk gastrointestinal stromal tumors characterized for c-kit and platelet-derived growth factor receptor alpha gene alterations. Cancer 104(1):159-169
127. Ricci R, Arena V, Castri F et al (2004) Role of p16/INK4a in gastrointestinal stromal tumor progression. Am J Clin Pathol 122 (1):35-43 (Pubitemid 38849870)
128. Sabah M, Cummins R, Leader M et al (2004) Loss of heterozygosity of chromosome 9p and loss of p16INK4A expression are associated with malignant gastrointestinal stromal tumors. Mod Pathol 17(11):1364-1371
129. Schneider-Stock R, Boltze C, Lasota J et al (2003) High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol 21(9):1688-1697
130. Schneider-Stock R, Boltze C, Lasota J et al (2005) Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study. Clin Cancer Res 11(2 Pt 1):638-645
131. Steigen SE, Bjerkehagen B, Haugland HK et al (2008) Diagnostic and prognostic markers for gastrointestinal stromal tumors in Norway. Mod Path 21(1):46-53
132. Feakins RM (2005) The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated with anatomical site, and p53 expression is associated with grade and clinical outcome. Histopathology 46(3):270-279
133. Nemoto Y, Mikami T, Hana K et al (2006) Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: relevance of cellularity and p27kip1. Pathol Int 56(12):724-731
134. Pruneri G, Mazzarol G, Fabris S et al (2003) Cyclin D3 immunoreactivity in gastrointestinal stromal tumors is independent of cyclin D3 gene amplification and is associated with nuclear p27 accumulation. Mod Path 16(9):886-892
135. Tornillo L, Duchini G, Carafa V et al (2005) Patterns of gene amplification in gastrointestinal stromal tumors (GIST). Lab Invest 85(7):921-931
136. Romeo S, Debiec-Rychter M, Van Glabbeke M et al (2009) Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res 15(12):4191-4198
137. Martinho O, Gouveia A, Silva P et al (2009) Loss of RKIP expression is associated with poor survival in GISTs. Virchows Arch 455(3):277-284
138. Turkoz HK, Alkan I, Sisman S et al (2009) Cyclooxygenase-2 expression and connection with tumor recurrence and histopathologic parameters in gastrointestinal stromal tumors. APMIS 117 (11):825-830
139. Wei YC, Li CF, Yu SC et al (2009) Ezrin overexpression in gastrointestinal stromal tumors: an independent adverse prognosticator associated with the non-gastric location. Mod Path 22 (10):1351-1360
140. Blanke CD, Demetri GD, von Mehren M et al (2008) Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 26(4):620-625 (Pubitemid 351264357)
141. Blanke CD, Rankin C, Demetri GD et al (2008) Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 26(4):626-632
142. Heinrich MC, Corless CL, Blanke CD et al (2006) Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24(29):4764-4774
143. Casali PG, Jost L, Reichardt P et al (2008) Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 19(Suppl 2):ii35-ii38
144. DeMatteo R, Owzar K, Antonescu C R, et al. (2008). Efficacy of adjuvant imatinib mesylate following complete resection of localized, primary gastrointestinal stromal tumor (GIST) at high risk of recurrence: the US intergroup phase II trial ACOSOG Z9000. Gastrointestinal Cancer Symposium, Orlando, Florida. Proceedings No. 8, p73
145. DeMatteo RPACR, Chadaram V, et al. (2005). Adjuvant imatinib mesylate in patients with primary high risk gastrointestinal stromal tumors (GIST) following complete resection: Safety results from the U.S. Intergroup Phase II trial ACOSOG Z9000. J Clin Oncol 23(ASCO Annual Meeting Proceedings. No. 16S, Part I of II (June 1 Supplement))
146. 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(9669):1097-1104
147. Lasota J, Miettinen M (2006) KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol 23 (2):91-102
148. Fletcher J, Corless C, Dimitrijevic S et al. (2003) Mechanisms of resistance to imatinib mesylate (IM) in advanced gastrointestinal stromal tumors (GIST). Proc Am Soc Clin Oncol (22):3275-3277
149. Debiec-Rychter M, Cools J, Dumez H et al (2005) Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinibresistant mutants. Gastroenterology 128(2):270-279
150. Liegl B, Kepten I, Lee C et al (2008) Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 216(1):64-74
151. Agaram NP, Besmer P, Wong GC et al (2007) Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive gastrointestinal stromal tumors. Clin Cancer Res 13(1):170-181
152. Prenen H, Cools J, Mentens N et al (2006) Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 12(8):2622-2627
153. Wardelmann E, Merkelbach-Bruse S, Pauls K et al (2006) Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 12(6):1743-1749
154. Antonescu CR, Besmer P, Guo T et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11(11):4182-4190
155. 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(9544):1329-1338
156. Montemurro M, Schoffski P, Reichardt P et al (2009) Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer 45 (13):2293-2297
157. Dewaele B, Wasag B, Cools J et al (2008) Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumorassociated PDGFRAD842V mutation. Clin Cancer Res 14 (18):5749-5758
158. Muhlenberg T, Zhang Y, Wagner AJ et al (2009) Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors. Cancer Res 69(17):6941-6950
159. Pantaleo MA, Astolfi A, Di Battista M et al (2009) Insulin-like growth factor 1 receptor expression in wild-type GISTs: a potential novel therapeutic target. Int J Cancer 125(12):2991-2994
160. Tarn C, Rink L, Merkel E et al (2008) Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci U S A 105(24):8387-8392
161. Bauer S, Yu LK, Demetri GD et al (2006) Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res 66(18):9153-9161
162. Sambol EB, Ambrosini G, Geha RC et al (2006) Flavopiridol targets c-KIT transcription and induces apoptosis in gastrointestinal stromal tumor cells. Cancer Res 66(11):5858-5866
163. Bauer S, Parry JA, Muhlenberg T et al (2010) Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells. Cancer Res 70(1):150-159
164. Bauer S, Duensing A, Demetri GD et al (2007) KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene 26(54):7560-7568
165. Ou WB, Zhu MJ, Demetri GD et al (2008) Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors. Oncogene 18:5624-5634