Dematteo Ronald P, Gold Jason S, Saran Lisa, Gönen Mithat, Liau Kui Hin, Maki Robert G, Singer Samuel, Besmer Peter, Brennan Murray F, Antonescu Cristina R
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer. 2008 Feb 1;112(3):608-15. doi: 10.1002/cncr.23199.
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-of-function 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 KIT mutation in primary GIST.
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 KIT mutation was found in 71% of patients and a PDGFRA mutation in 6%.
After a median follow-up of 4.7 years, recurrence-free survival was 83%, 75%, and 63% at 1, 2, and 5 years, respectively. On multivariate analysis recurrence was predicted by > or =5 mitoses/50 high-power fields, tumor size > or =10 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, 6.5-32.4). Specific KIT mutations had prognostic importance by univariate but not multivariate analysis. Patients with KIT exon 11 point mutations and insertions had a favorable prognosis. Those with KIT exon 9 mutations or KIT 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.
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.
胃肠道间质瘤（GIST）是肠道最常见的肉瘤，由于功能获得性突变，常表现为KIT或血小板衍生生长因子受体α（PDGFRA）受体酪氨酸激酶的组成性激活。尽管酪氨酸激酶抑制剂在转移性GIST中的疗效取决于肿瘤突变状态，但关于KIT突变在原发性GIST中的预后重要性一直存在相互矛盾的报道。
共研究了127例1983年至2002年就诊于本机构的局限性原发性GIST患者，这些患者均接受了疾病的完整大体手术切除。大多数肿瘤起源于胃（58%）或小肠（28%）。通过聚合酶链反应（PCR）和直接测序，在71%的患者中发现了KIT突变，6%的患者中发现了PDGFRA突变。
中位随访4.7年后，1年、2年和5年的无复发生存率分别为83%、75%和63%。多因素分析显示，复发的预测因素为≥5个核分裂象/50个高倍视野、肿瘤大小≥10 cm以及肿瘤位置（小肠GIST患者预后最差）。特别是，高核分裂率的风险比为14.6（95%置信区间，6.5 - 32.4）。单因素分析显示特定的KIT突变具有预后重要性，但多因素分析未显示。KIT外显子11点突变和插入的患者预后良好。KIT外显子9突变或涉及氨基酸W557和/或KSS8的KIT外显子11缺失的患者复发率较高，而无酪氨酸激酶突变的患者预后中等。
在未使用酪氨酸激酶抑制剂治疗的情况下，完全切除的原发性GIST的复发可通过核分裂率、肿瘤大小和肿瘤位置独立预测。
