Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival

Modern Pathology

Volumn 24, Issue 2, 2011, Pages 248-255

  Haller, Florian ^a,d   Cortis, Judith ^a   Helfrich, Joel ^a   Cameron, Silke ^a   Schüler, Philipp ^a   Schwager, Stefanie ^a   Gunawan, Bastian ^a,c   Füzesi, László ^a   Agaimy, Abbas ^b  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c Helios Klinikum   (Germany)

^d UNIVERSITY OF FREIBURG   (Germany)

Author keywords

epithelioid; GIST; KIT mutation; phenotype

Indexed keywords

BIOLOGICAL MARKER; CYCLIN B1; KI 67 ANTIGEN;

ANATOMY; ARTICLE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE PHASE; CELL CYCLE S PHASE; CONTROLLED STUDY; DISEASE FREE SURVIVAL; EPITHELIOID CELL; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; GENOTYPE; HUMAN; HUMAN TISSUE; KIT GENE; LARGE INTESTINE; MITOSIS; MORPHOLOGY; ONCOGENE; PDGFRA GENE; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; SMALL INTESTINE; STOMACH; TISSUE MICROARRAY; TUMOR GROWTH; TUMOR VOLUME;

CELL CYCLE; DISEASE-FREE SURVIVAL; EPITHELIOID CELLS; GASTROINTESTINAL STROMAL TUMORS; GENOTYPE; HUMANS; IMMUNOHISTOCHEMISTRY; MUTATION; PHENOTYPE; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-KIT; STOMACH NEOPLASMS; TISSUE ARRAY ANALYSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 79551625851     PISSN: 08933952     EISSN: 15300285     Source Type: Journal    
DOI: 10.1038/modpathol.2010.188     Document Type: Article

References (23)

1. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002;33:459-465. (Pubitemid 34747864)
2. 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;29:52-68.
3. 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: 477-489.
4. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-580. (Pubitemid 28067289)
5. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003;299:708-710.
6. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:70-83.
7. 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 2004;6:197-204.
8. 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;84:874-883.
9. Yu CC, Fletcher CD, Newman PL, et al. A comparison of proliferating cell nuclear antigen (PCNA) immunostaining, nucleolar organizer region (AgNOR) staining, and histological grading in gastrointestinal stromal tumors. J Pathol 1992;166:147-152.
10. 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;20:3898-3905.
11. 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;6:39-48.
12. Rutkowski P, Nowecki ZI, Michej W, et al. Risk criteria and prognostic factors for predicting recurrences after resection of primary gastrointestinal stromal tumor. Ann Surg Oncol 2007;14:2018-2027.
13. Wasag B, Debiec-Rychter M, Pauwels P, et al. Differential expression of KIT/PDGFRA mutant isoforms in epithelioid and mixed variants of gastrointestinal stromal tumors depends predominantly on the tumor site. Mod Pathol 2004;17:889-894.
14. Penzel R, Aulmann S, Moock M, et al. The location of KIT and PDGFRA gene mutations in gastrointestinal stromal tumors is site and phenotype associated. J Clin Pathol 2005;58:634-639.
15. Lasota J, Stachura J, Miettinen M. GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology. Lab Invest 2006;86:94-100.
16. Agaimy A, Haller F, Gunawan B, et al. Distinct biphasic histomorphological pattern in gastrointestinal stromal tumors (GISTs) with common primary mutations but divergent molecular cytogenetic progression. Histopathology 2009;54:295-302.
17. Haller F, Gunawan B, von Heydebreck A, et al. Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors. Clin Cancer Res 2005;11:6589-6597.
18. Cameron S, Haller F, Dudas J, et al. Immune cells in primary gastrointestinal stromal tumors. Eur J Gastroenterol Hepatol 2008;20:327-334.
19. Kawanowa K, Sakuma Y, Sakurai S, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol 2006;37: 1527-1535.
20. Agaimy A, Wünsch 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;31:113-120.
21. Abraham SC, Krasinskas AM, Hofstetter WL, et al. 'Seedling' mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. Am J Surg Pathol 2007;31:1629-1635.
22. Schneider-Stock R, Boltze C, Lasota J, et al. High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol 2003;21:1688-1697.
23. Haller F, Löbke C, Ruschhaupt M, et al. Loss of 9p leads to p16INK4A down-regulation and enables RB/E2F1- dependent cell cycle promotion in gastrointestinal stromal tumors (GISTs). J Pathol 2008;215:253-262.