腹腔内胃肠道外间质瘤基因突变和预后因素的研究

Gene mutation and prognosis of extragastrointestinal stromal tumor

目的探讨腹腔内胃肠道外间质瘤（EGIST）中c-kit和血小板衍生生长因子受体α（PDGFR-α）基因突变、临床病理特征和预后的影响因素。方法应用免疫组织化学方法检测23例EGIST中CD117、CD34和Ki-67蛋白的表达，应用PCR扩增和基因测序的方法检测c-kit和PDGFR-α基因突变，结合临床病理特征分析影响EGIST患者预后的相关因素。采用Kaplan-Meier法和COX比例风险模型比较不同因素对生存的影响。结果本组c-kit基因的突变率为44％，均为第11号外显子突变；PDGFR-α基因的突变率是13％，均为第18号外显子的突变（D842V点突变）。CD117表达阳性率是100％，CD34表达阳性率为74％。Ki-67指数：〈1％者占30％，1％-5％者占44％，〉5％者占26％。生存分析显示，核分裂象数目（P=0．025）和Ki-67指数（P=0．032）与疾病相关生存时间相关。结论EGIST有着与GIST相似的c-kit和PDGFR-α基因突变位点，并且c-kit基因突变频率也相近，但是PDGFR-α基因突变频率较GIST稍高。可以将EGIST作为GIST的一个特殊亚型。结合核分裂象和Ki-67指数对EGIST进行分级是判断预后的一个较好的标准。

Objective To evaluate prognostic significance of c-kit and PDGFR-α gene mutation in extragastrointestinal stromal tumors （EGIST）. Methods Paraffin embedded tissue specimens from 23 EGISTs were tested for CD117, CD34 and Ki-67 expression by immunohistochemical method. EGIST cases were also tested for the presence of c-kit exons 9, 11,13,17 mutations and PDGFR-α exons 12, 18 mutations. Kaplan-meier survival rate was used to evaluate the prognostic factors. Results Of 23 cases of EGIST, 23（ 100% ） were positive for CD117, 17（74% ） were positive for CD34. For Ki-67 labeling index （Ki-67 LI）： 30% were 〈 1%, 44% were between 1% -5%, 26% were 〉5%. C-kit mutations were detected in 44% of EGIST patients and all were of exon 11 mutations. PDGFR-α mutations were found in 13% of all the 23 cases and all were of exon 18 mutations （The commonest type of mutation D842V）. Survival analysis indicated that mitotic count and Ki-67 index were significant predictors for survival. Conclusion The pattern of c-kit and PDGFR-α mutation in EGIST was essentially similar to that in GIST. But the mutation frequency of PDGFR-α was slightly higher in EGIST than in GIST. EGIST could be a special subtype of GIST. The results of this study also show combination of mitotic counts and Ki-67 labeling index may be useful for predicting the prognosis of EGIST.