{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:10:49Z","timestamp":1791943849382,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T00:00:00Z","timestamp":1197417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal tract and often shows constitutive activation of either the KIT or PDGFRA receptor tyrosine kinases because of gain\u2010of\u2010function mutation. Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of <jats:italic>KIT<\/jats:italic> mutation in primary GIST.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>A total of 127 patients were studied who presented to our institution from 1983 to 2002 with localized primary GIST and underwent complete gross surgical resection of disease. The majority of tumors originated in the stomach (58%) or small intestine (28%). By using polymerase chain reaction (PCR) and direct sequencing, a <jats:italic>KIT<\/jats:italic> mutation was found in 71% of patients and a <jats:italic>PDGFRA<\/jats:italic> mutation in 6%.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>After a median follow\u2010up of 4.7 years, recurrence\u2010free survival was 83%, 75%, and 63% at 1, 2, and 5 years, respectively. On multivariate analysis recurrence was predicted by \u22655 mitoses\/50 high\u2010power fields, tumor size \u226510 cm, and tumor location (with patients having small bowel GIST doing the worst). In particular, a high mitotic rate conferred a hazard rate of 14.6 (95% confidence interval, 6.5\u201332.4). Specific <jats:italic>KIT<\/jats:italic> mutations had prognostic importance by univariate but not multivariate analysis. Patients with <jats:italic>KIT<\/jats:italic> exon 11 point mutations and insertions had a favorable prognosis. Those with <jats:italic>KIT<\/jats:italic> exon 9 mutations or <jats:italic>KIT<\/jats:italic> exon 11 deletions involving amino acid W557 and\/or K558 had a higher rate of recurrence, whereas patients without a tyrosine kinase mutation had intermediate outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>In the absence of therapy with tyrosine kinase inhibitors, recurrence in completely resected primary GIST is independently predicted by mitotic rate, tumor size, and tumor location. Cancer 2008. \u00a9 2007 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.23199","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T11:16:29Z","timestamp":1197458189000},"page":"608-615","source":"Crossref","is-referenced-by-count":371,"title":["Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST)"],"prefix":"10.1002","volume":"112","author":[{"given":"Ronald P.","family":"DeMatteo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Saran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithat","family":"G\u00f6nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui Hin","family":"Liau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Maki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Besmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray F.","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina R.","family":"Antonescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,12]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.043"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079666"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1037763100"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0891"},{"key":"e_1_2_5_6_2","article-title":"Outcome of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate: Four\u2010year follow\u2010up of a phase II randomized trial","author":"Blanke CD","year":"2006","journal-title":"Gastrointest Cancers Symp."},{"issue":"16","key":"e_1_2_5_7_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/jco.2005.23.16_suppl.7","article-title":"Correlation of target kinase genotype with clinical activity of imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT (KIT+)","volume":"23","author":"Heinrich MC","year":"2005","journal-title":"J Clin Oncol."},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.01.030"},{"key":"e_1_2_5_9_2","first-page":"1633","article-title":"KIT mutation portends poor prognosis in gastrointestinal stromal\/smooth muscle tumors","volume":"78","author":"Ernst SI","year":"1998","journal-title":"Lab Invest."},{"key":"e_1_2_5_10_2","first-page":"4297","article-title":"Effect of c\u2010kit mutation on prognosis of gastrointestinal stromal tumors","volume":"59","author":"Taniguchi M","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0581"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i25.3948"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.19.554"},{"key":"e_1_2_5_14_2","first-page":"1361","article-title":"Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach","volume":"28","author":"Cho S","year":"2006","journal-title":"Int J Oncol."},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61103-0"},{"key":"e_1_2_5_16_2","first-page":"3329","article-title":"Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors","volume":"9","author":"Antonescu CR","year":"2003","journal-title":"Clin Cancer Res."},{"key":"e_1_2_5_17_2","first-page":"261","article-title":"Dominant negative and loss of function mutations of the c\u2010kit (mast\/stem cell growth factor receptor) proto\u2010oncogene in human piebaldism","volume":"50","author":"Spritz RA","year":"1992","journal-title":"Am J Hum Genet."},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000157790.81329.47"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-200001000-00008"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.5350"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-6-29"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2003.01665.x"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10434-001-0050-4"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s101200300005"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199901000-00009"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000146010.92933.de"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700360"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.03.095"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000097365.72526.3E"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(03)00407-6"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64623-8"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2001.tb01121.x"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11323"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1309\/AKK3VFF610CWM566"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700122"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/00313020400023628"},{"key":"e_1_2_5_37_2","first-page":"815","article-title":"Mechanisms of resistance to imatinib mesylate (IM) in advanced gastrointestinal stromal tumor (GIST)","volume":"22","author":"Fletcher JA","year":"2003","journal-title":"Proc Am Soc Clin Oncol."},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0085"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.11.020"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2245"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020461"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2558"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441404"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17098-0"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.23199","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.23199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:42:59Z","timestamp":1760305379000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.23199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,12]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,2]]}},"alternative-id":["10.1002\/cncr.23199"],"URL":"https:\/\/doi.org\/10.1002\/cncr.23199","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,12]]}}}