Miettinen Markku, El-Rifai Wa'el, H L Sobin Leslie, Lasota Jerzy
Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Hum Pathol. 2002 May;33(5):478-83. doi: 10.1053/hupa.2002.124123.
This paper reviews data on the prognosis of gastrointestinal stromal tumors (GISTs). These tumors are specific KIT-expressing and KIT-signaling-driven mesenchymal tumors, many of which have KIT-activating mutations. GISTs occur in the entire gastrointestinal (GI) tract and may also arise from the omentum, mesenteries, and retroperitoneum. They range from small benign tumors to sarcomas at all sites of occurrence. A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Understanding the natural history of GIST before introduction of STI-571 will help assess the impact and position of this new treatment. The frequency of benign versus malignant GISTs varies between sites. Benign GISTs outnumber malignant GISTs in the stomach, whereas malignant GISTs are more common in the intestines. Tumors that have metastasized at presentation have a very poor prognosis. Traditionally, the 3 key prognostic factors have been mitotic rate, tumor size, and site. Tumors that are small (< or =2 cm) and show mitotic activity not exceeding 5 mitoses per 50 high-power fields (HPFs) have an excellent prognosis, probably independent of site, although this has not been shown specifically for all sites. In the stomach, most epithelioid GISTs are benign, provided that mitotic counts do not exceed 5/50 HPFs. However, a small proportion of tumors apparently lacking mitotic activity do metastasize. Tumors with a mitotic rate >5/50 HPFs usually have a malignant behavior. The Ki67 index may help identify tumors with malignant potential, but large site-specific series are not yet available. Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential.
本文综述了胃肠道间质瘤（GISTs）的预后数据。这些肿瘤是特定表达KIT和由KIT信号驱动的间充质肿瘤，其中许多具有KIT激活突变。GISTs发生于整个胃肠道（GI），也可能起源于网膜、肠系膜和腹膜后。它们在所有发生部位的范围从小的良性肿瘤到肉瘤。一种KIT酪氨酸激酶抑制剂STI-571（伊马替尼[格列卫]；瑞士巴塞尔诺华公司）最近在转移性GISTs的治疗中显示出前景。在引入STI-571之前了解GIST的自然病史将有助于评估这种新治疗的影响和地位。良性与恶性GISTs的发生率在不同部位有所不同。胃中良性GISTs的数量超过恶性GISTs，而恶性GISTs在肠道中更常见。就诊时已发生转移的肿瘤预后很差。传统上，3个关键的预后因素是有丝分裂率、肿瘤大小和部位。小的（≤2 cm）且每50个高倍视野（HPFs）有丝分裂活性不超过5个有丝分裂的肿瘤预后极佳，可能与部位无关，尽管尚未针对所有部位具体证实这一点。在胃中，大多数上皮样GISTs是良性的，前提是有丝分裂计数不超过5/50 HPFs。然而，一小部分明显缺乏有丝分裂活性的肿瘤确实会发生转移。有丝分裂率>5/50 HPFs的肿瘤通常具有恶性行为。Ki67指数可能有助于识别具有恶性潜能的肿瘤，但尚未有针对特定部位的大型系列研究。包括DNA拷贝数变化、端粒酶活性和KIT突变状态在内的基因标志物可能有助于更准确地识别具有恶性潜能的肿瘤。
