Assessing the prognosis of gastrointestinal stromal tumors: a growing role for molecular testing.
Assessing the prognosis of gastrointestinal stromal tumors: a growing role for molecular testing.
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评估胃肠道间质瘤的预后：分子检测的作用日益增强。
DOI：
10.1309/buvlrqbvgu0n0l42
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发表时间：
2004
影响因子：
3.5
通讯作者：
C. Corless
中科院分区：
文献类型：
--
作者：
C. Corless
近年来，KIT（CD 117）的免疫组化分析已使胃肠道间质瘤（GIST）的诊断变得几乎常规化。这一点尤其重要，因为现在有一种有效的治疗方法-激酶抑制剂甲磺酸伊马替尼（格列卫）治疗-可用于不可切除或广泛转移性疾病的患者。1，2肿瘤学家有时仍然担心GIST的诊断被忽视，但最近对KIT染色的关注可能导致过度诊断而不是错过治疗机会。尽管GIST具有形态学（上皮样、多形性）和免疫表型（KIT弱或阴性）特征，但这些仅代表少数病例。4目前GIST更大的问题是确定其预后而不是做出诊断。过去几十年关于“良性”和“恶性”GIST之间区别的大辩论基本上已经得到解决，支持所有GIST都有恶性潜力的观点;这只是一个程度问题。因此，短语“恶性潜能不确定的间质瘤（STUMP）”仍然适用于典型的原发性GIST，尽管必须强调的是，难倒的是病理学家，而不是肿瘤。为了强调胃肠道间质瘤的恶性潜能，该领域的许多专家通常将其诊断为胃肠道间质瘤，这是一种谨慎的诊断，但对临床医生和患者的指导相对较少。那么，如何最好地评估新诊断的原发性GIST患者的预后？有许多参数已被定义为在GIST中可重复地具有重要的病理学意义，包括大小、有丝分裂指数、粘膜溃疡、坏死、起源部位和非整倍性。其中，大小和有丝分裂指数是大多数已发表方案中强调的特征，包括在2001年4月举行的国立卫生研究院-国立癌症研究所主办的研讨会之后发表的共识指南。（600例），Kindblom及其同事的回顾性流行病学研究，6，其中发现低风险和极低风险肿瘤患者的长期生存率与一般人群几乎相同。毫不奇怪，占总数20%至30%的高风险和明显恶性肿瘤的预后要差得多。然而，即使在这些群体中，也有长期幸存者（>15年）。对于中危病变患者，生存率更接近于低危组而非高危组。这项重要的研究是后KIT时代的第一项研究，证实了关于GIST的两个一般性观察：（1）绝大多数极低风险，低风险和中等风险的GIST表现良好。(2)在这些肿瘤中，有一个不可预测的子集表现出侵略性。类似的研究正在进行中，可能会导致对共识准则的微调。然而，值得怀疑的是，任何仅基于肿瘤大小和有丝分裂指数的方案都将允许临床医生在遇到典型的原发性GIST患者时，用任何比模糊的法律用语（“史密斯先生，很可能是......”）更多的东西来解释病理报告。当复发性或转移性GIST没有有效的治疗方法时，这种不确定性是可以容忍的（化疗和放疗对这种疾病不起作用）。然而，随着伊马替尼的引入，GIST的风险评估具有新的重要性。晚期GIST患者的预后在伊马替尼治疗后发生了显著变化。
In recent years, immunohistochemical analysis for KIT (CD117) has made the once troublesome diagnosis of gastrointestinal stromal tumor (GIST) almost routine in most cases. This is particularly important now that an effective therapy—treatment with the kinase inhibitor imatinib mesylate (Gleevec)—is available for patients with unresectable or widely metastatic disease.1,2 Oncologists still sometimes fret that a diagnosis of GIST has been overlooked, but the recent attention given to KIT staining probably has resulted more in overdiagnosis than in missed opportunities to treat.3 Although there are GISTs with unusual morphologic (epithelioid, pleomorphic) and immunophenotypic (KIT weak or negative) characteristics, these represent only a minority of cases.4 The greater problem with GISTs today is in determining their prognosis rather than making their diagnosis. Great debates of past decades about the distinction between “benign” and “malignant” GISTs largely have been resolved in favor of the view that all GISTs have malignant potential; it is just a question of degree. Thus, the phrase “stromal tumor of uncertain malignant potential (STUMP)” still applies to the typical primary GIST, although it must be emphasized that it is the pathologist who is stumped, not the tumor. To stress the malignant potential of GISTs, many experts in the field routinely sign them out as gastrointestinal stromal sarcoma—a prudent diagnosis that nevertheless offers relatively little guidance to clinicians and their patients. How best, then, to assess the prognosis of a patient with a newly diagnosed primary GIST? There are a number of parameters that have been defined reproducibly as prognostically important in GISTs, including size, mitotic index, mucosal ulceration, necrosis, site of origin, and aneuploidy. Among these, size and mitotic index are the features emphasized in most published schemes, including the consensus guidelines published after a National Institutes of Health–National Cancer Institute–sponsored workshop held in April 2001.5 These guidelines recently were used in a large (600 cases), retrospective epidemiologic study by Kindblom and colleagues,6 in which it was found that the long-term survival of patients with low-risk and very-low-risk tumors was almost the same as that of the general population. Not surprisingly, high-risk and overtly malignant tumors, which constituted 20% to 30% of the total, had a much poorer prognosis. Yet even among these groups, there were long-term survivors (>15 years). For patients with intermediate-risk lesions, the survival was closer to that of the low-risk group than the highrisk group. This important study, the first in the post-KIT era, confirms 2 general observations about GISTs: (1) The great majority of very-low-risk, low-risk, and intermediate-risk GISTs behave in a benign manner. (2) Among these tumors, there is an unpredictable subset that behaves aggressively. Similar studies are ongoing and perhaps will result in fine-tuning of the consensus guidelines. It is doubtful, however, that any scheme based solely on tumor size and mitotic index will permit the clinician, when meeting a patient with a typical primary GIST, to interpret the pathology report with anything more than vaguely legalistic phrases (“Mr Smith, it is more likely than not that....”). Such uncertainty was tolerable when there were no effective therapies for recurrent or metastatic GISTs (chemotherapy and radiation treatment do not work in this disease). With the introduction of imatinib, however, risk assessment of GISTs has taken on new importance. The prognosis of patients with advanced GISTs has changed dramatically with imatinib therapy.1,2 Based on an