Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations
Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations
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DOI：
10.1038/gim.2014.115
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发表时间：
2015-05-01
影响因子：
8.8
通讯作者：
Biasco, Guido
中科院分区：
文献类型：
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作者：
Pantaleo, Maria A.;Lolli, Cristian;Biasco, Guido
目的：部分KIT/PDGFRA野生型胃肠道间质瘤患者表现出琥珀酸脱氢酶功能的丧失，主要是由于琥珀酸脱氢酶亚单位的胚系突变，其中以琥珀酸脱氢酶A亚单位为主。这些患者的临床结果似乎是好的，据报道，这些患者在小系列报道中被单独描述。方法：69例转移性胃肠道间质瘤患者，其中KIT/PDGFRA野生型11例，其中6例为琥珀酸脱氢酶缺陷型，5例为非琥珀酸脱氢酶缺陷型，58例为KIT/PDGFRA突变型。所有六名琥珀酸脱氢酶缺陷患者都存在SDHA突变。采用Kaplan-Meier曲线和LOG-RANK检验比较琥珀酸脱氢酶A亚基突变的胃肠道间质瘤患者与无琥珀酸脱氢酶缺陷的KIT/PDGFRA野生型患者和KIT/PDGFRA突变的胃肠道间质瘤患者的生存期。从不同角度分析，琥珀酸脱氢酶A亚基突变的胃肠道间质瘤与KIT/PDGFRA突变或KIT/PDGFRA野生型非琥珀酸脱氢酶缺陷型胃肠道间质瘤之间的差异有统计学意义(从整个研究人群的胃肠道间质瘤的诊断来看，分别为P=0.007和P=0.033；从整个研究人群的转移性疾病的诊断来看，分别为P=0.005和P=0.018；结论：转移性KIT/PDGFRA野生型琥珀酸脱氢酶缺陷的胃肠道间质瘤携带琥珀酸脱氢酶亚单位A突变的患者具有令人印象深刻的长生存期。应该在临床实践中识别这些患者，以便随着时间的推移更好地量身定制治疗和随访。
Purpose: A subset of patients with KIT/PDGFRA wild-type gastrointestinal stromal tumors show loss function of succinate dehydrogenase, mostly due to germ-line mutations of succinate dehydrogenase subunits, with a predominance of succinate dehydrogenase subunit A. The clinical outcome of these patients seems favorable, as reported in small series in which patients were individually described. This work evaluates a retrospective survival analysis of a series of patients with metastatic KIT/PDGFRA wild-type succinate dehydrogenase-deficient gastrointestinal stromal tumors.Methods: Sixty-nine patients with metastatic gastrointestinal stromal tumors were included in the study (11 KIT/PDGFRA wild-type, of whom 6 were succinate dehydrogenase deficient, 5 were non-succinate dehydrogenase deficient, and 58 were KIT/PDGFRA mutant). All six succinate dehydrogenase-deficient patients harbored SDHA mutations. Kaplan-Meier curves and log-rank tests were used to compare the survival of patients with succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors with that of KIT/PDGFRA wild-type patients without succinate dehydrogenase deficiency and patients with KIT/PDGFRA-mutant gastrointestinal stromal tumors.Results: Follow-up ranged from 8.5 to 200.7 months. The difference between succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors and KIT/PDGFRA-mutant or KIT/PDGFRA wild-type non-succinate dehydrogenase deficient gastrointestinal stromal tumors was significant considering different analyses (P = 0.007 and P = 0.033, respectively, from diagnosis of gastrointestinal stromal tumor for the whole study population; P = 0.005 and P = 0.018, respectively, from diagnosis of metastatic disease for the whole study population; P = 0.007 for only patients who were metastatic at diagnosis).Conclusion: Patients with metastatic KIT/PDGFRA wild-type -succinate dehydrogenase-deficient gastrointestinal stromal tumors harboring succinate dehydrogenase subunit A mutations present an impressively long survival. These patients should be identified in clinical practice to better tailor treatments and follow-up over time.