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目的探讨胃肠道间质瘤(GIST)的生物学行为,分析临床病理特征对于 GIST 患者生存率的影响,同时检测 c-kit 基因11号外显子的突变,试图发现对 GIST 预后判断有意义的指标。方法收集解放军总医院病理科156例发生于胃与小肠的 GIST,总结临床病理特征包括年龄、临床分期、肿瘤直径、核分裂象计数、坏死、风险分级等,并进行统计学分析。套式 PCR 扩增 c-kit 基因11号外显子,变性高效液相色谱法筛查,并进行 DNA 直接测序检测突变。结果胃 GIST 83例,平均年龄55.4岁,62例获得随访,17例复发或转移,5年生存率为66.5%±17.1%。小肠 GIST 73例,平均年龄50.6岁,43例获得随访,22例发生复发或转移,5年生存率为61.8%±18.3%。对于胃 GIST 患者,年龄小于50岁(P=0.046),临床分期晚(P=0.0001),肿瘤直径大(P=0.0001),核分裂象计数多(P=0.0001),肿瘤组织出现坏死(P=0.0001)和风险分级高(P=0.004)提示生存率低。COX 风险比例模型发现临床分期晚(P=0.001)、肿瘤直径大(P=0.001)、核分裂象计数多(P=0.002)、风险分级高(P=0.018)与患者预后差相关。在小肠 GIST 中,肿瘤组织坏死(P=0.036)、临床分期晚(P=0.010)与患者生存率低相关,其中临床分期为独立的预后提示因子。c-kit 基因11号外显子突变检测发现共25例患者存在突变,胃 GIST 的突变率为32.0%,主要发生于50岁以上患者,小肠GIST 的突变率为22.5%,主要发生于40～49岁患者。结论根据临床病理特征可以对 GIST 患者的预后进行判断,其中胃 GIST 患者可以根据临床分期、肿瘤直径、核分裂象计数、风险分级来削断预后,小肠 GIST 患者可依据临床分期及肿瘤组织坏死来判断预后。小肠 GIST 比胃 GIST 更易复发或转移。胃与小肠 GIST 基因的突变可能与患者的年龄相关。
OBJECTIVE: To investigate the biological behavior of gastrointestinal stromal tumors (GISTs) and to analyze the clinicopathological characteristics of patients with GIST, and to detect the mutation of exon 11 of c-kit gene in order to find out the significance of GIST prognosis index. Methods A total of 156 patients with GIST in the stomach and small intestine were collected from the Department of Pathology, PLA General Hospital. The clinical and pathological features including age, clinical stage, tumor diameter, mitotic figures, necrosis and risk grade were collected and analyzed statistically. Nested c-kit gene exon 11 was amplified by nested PCR, denatured by high performance liquid chromatography, and DNA sequencing was used to detect the mutations. Results 83 cases of gastric GIST with an average age of 55.4 years, 62 cases were followed up, 17 cases of recurrence or metastasis, 5-year survival rate was 66.5% ± 17.1%. Small intestinal GIST 73 cases, mean age 50.6 years old, 43 cases were followed up, 22 cases of recurrence or metastasis, 5-year survival rate was 61.8% ± 18.3%. For patients with gastric GIST, age less than 50 years old (P = 0.046), clinical stage (P = 0.0001), tumor diameter (P = 0.0001), mitosis count (P = 0.0001), tumor necrosis (P = 0.0001) and a higher risk rating (P = 0.004) suggested a lower survival rate. COX risk proportional model found that the clinical stage (P = 0.001), large tumor diameter (P = 0.001), mitotic count more (P = 0.002), higher risk classification (P = 0.018) correlated with poor prognosis. Tumor tissue necrosis (P = 0.036) and late clinical stage (P = 0.010) were associated with low survival in small intestine GIST, with clinical stage as an independent prognostic cue. The mutation of exon 11 of c-kit gene was detected in 25 patients. The mutation rate of gastric GIST was 32.0%, which mainly occurred in patients over 50 years old. The mutation rate of intestinal GIST was 22.5%, which mainly occurred in 40-49 Aged patient Conclusions The prognosis of patients with GIST can be judged according to the clinicopathological features. The prognosis of patients with GIST can be judged according to clinical stage, tumor diameter, mitosis count and risk grade. Small intestinal GIST patients can be judged according to clinical stage and tumor necrosis Prognosis. Small intestinal GIST is more likely to relapse or metastasize than gastric GIST. Mutations in the stomach and small intestine GIST genes may be related to the patient’s age.