Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST)
Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST)
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DOI：
10.1002/cncr.23199
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发表时间：
2008-02-01
期刊：
影响因子：
6.2
通讯作者：
Antonescu, Cristina R.
中科院分区：
文献类型：
--
作者：
DeMatteo, Ronald P.;Gold, Jason S.;Antonescu, Cristina R.
背景胃肠道间质瘤（GIST）是最常见的肠道肉瘤，并且由于功能获得性突变而经常显示KIT或PDGFRA受体酪氨酸激酶的组成性激活。虽然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中的预后重要性的报道相互矛盾。我们研究了1983年至2002年期间来我院就诊的127例局限性原发性胃肠道间质瘤患者，并对其进行了完整的大体手术切除。大多数肿瘤起源于胃（58%）或小肠（28%）。采用聚合酶链反应（PCR）和直接测序法，在71%的患者中发现KIT突变，6%的患者中发现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%。在多变量分析中，预测复发的指标是核分裂≥ 5个/50个高倍视野，肿瘤大小≥ 10 cm，肿瘤位置（小肠GIST患者的预测最差）。特别是，高有丝分裂率的风险率为14.6（95%置信区间，6.5-32.4）。单变量分析显示特异性KIT突变具有预后重要性，但多变量分析无此意义。KIT 11号外显子点突变和插入的患者预后良好。KIT第9外显子突变或IGT第11外显子缺失涉及氨基酸W557和/或K558的患者复发率较高，而无酪氨酸激酶突变的患者的预后居中。在没有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的复发是由有丝分裂率、肿瘤大小和肿瘤位置独立预测的。
BACKGROUND. 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.METHODS. 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 7 1% of patients and a PDGFRA mutation in 6%.RESULTS. 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 >= 5 mitoses/50 high-power fields, tumor size >= 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 IGT 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.CONCLUSIONS. 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.