Qi Changsong, Pan Fang, Li Jian, Li Yanyan, Gao Jing, Shen Lin
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China.Email:
Zhonghua Wei Chang Wai Ke Za Zhi. 2018 Nov 25;21(11):1280-1284.
To investigate the biological behavior characteristics of gastrointestinal stromal tumors (GIST) with PDGFRA mutation and the patients' survival, and elucidate the efficacy of imatinib therapy.
Patients with PDGFRA D842V and non-D842V mutations were screened from a database of 1163 patients with GIST who were treated at Peking University Cancer Hospital from 2003 to 2018. Clinicopathological data of these patients were collected, including gender, age, tumor size, mitotic phase, primary position, metastatic site, and expressions of CD117, CD34, DOG-1. The association of gene mutations with biological behavior of GIST, prognosis of patients, and efficacy of imatinib therapy was examined. Fisher's exact test was used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used to analyze overall survival and recurrence-free survival.
A total of 27 patients with PDGFRA mutations were screened, among whom the D842V mutation was 1.6%(19/1 163), and the rate of non-D842V mutation was 0.7%(8/1 163). There were 11 male patients and 8 female patients of D842V mutation with male to female ratio of 1.38:1 and median age of 56 (35-72) years. There were 4 male patients and 4 female patients of non-D842V mutations with male to female ratio of 1:1 and median age of 51.5 (34-82) years. The primary lesions of D824V mutation were located in stomach for 18 cases and in parenteral area for 1 case. The primary lesions of non-D842V mutation were located in stomach for 6 cases, in jejunoileum for 1 case and in colorectum for 1 case. The proportion of nuclear fission <5/50 HPF in PDGFRA mutation GIST was 17/27. Among D842V mutation patients, mitotic phase <5/50 HPF accounted for 11/19, mitotic phase >10/50 HPF accounted for 3/19, and 5-10/50 HPF accounted for 5/19. Among non-D842V mutation patients, mitotic phase <5/50 HPF accounted for 6/8, 5-10/50 HPF accounted for 2/8. Of D842V mutation patients, positive CD117 was found in 15 cases(15/19); positive DOG-1 was found in 15 cases(15/19); positive CD34 was found in 16/17 cases. Among patients with non-D842V mutation, 7 patients were positive for CD117(7/8); only 5 patients were tested for CD34, and all 5 patients were positive(5/5); only 3 patients were tested for DOG-1, and all 3 cases were positive (3/3). The 3-year recurrence-free survival rate after radical resection in D842V mutation patients was 51.9%, and that in non-D842V mutation patients was 62.5% without significant difference(P=0.380). Recurrence-free rate did not decreased in patients with D842V mutation after adjuvant imatinib treatment and the benefit rate of first-line treatment with imatinib in patients with advanced disease was zero.
The PDGFRA gene mutation rate is low, mostly derived from gastric GIST. D842V and non-D842V mutations present inert biological behavior. D842V mutation GIST is resistant to imatinib, and non-D842V mutation GIST can obtain benefit from imatinib treatment.
探讨血小板衍生生长因子受体α（PDGFRA）突变的胃肠道间质瘤（GIST）生物学行为特征及患者生存情况，阐明伊马替尼治疗的疗效。
从2003年至2018年在北京大学肿瘤医院接受治疗的1163例GIST患者数据库中筛选出PDGFRA D842V和非D842V突变患者。收集这些患者的临床病理资料，包括性别、年龄、肿瘤大小、核分裂象、原发部位、转移部位以及CD117、CD34、DOG-1的表达情况。研究基因突变与GIST生物学行为、患者预后及伊马替尼治疗疗效的关系。采用Fisher确切概率法比较两组的临床特征。采用Kaplan-Meier法分析总生存和无复发生存情况。
共筛选出27例PDGFRA突变患者，其中D842V突变率为1.6%（19/1163），非D842V突变率为0.7%（8/1163）。D842V突变患者中男性11例，女性8例，男女比例为1.38:1，中位年龄为56（35 - 72）岁。非D842V突变患者中男性4例，女性4例，男女比例为1:1，中位年龄为51.5（34 - 82）岁。D824V突变的原发灶位于胃18例，位于非胃肠道区域1例。非D842V突变的原发灶位于胃6例，位于空肠回肠1例，位于结直肠1例。PDGFRA突变GIST中核分裂象<5/50 HPF的比例为17/27。在D842V突变患者中，核分裂象<5/50 HPF占11/19，核分裂象>10/50 HPF占3/19，5 - 10/50 HPF占5/19。在非D842V突变患者中，核分裂象<5/50 HPF占6/8，5 - 10/50 HPF占2/8。D842V突变患者中，CD117阳性15例（15/19）；DOG-1阳性15例（15/19）；CD34阳性16/17例。非D842V突变患者中，CD117阳性7例（7/8）；仅5例检测CD34，全部阳性（5/5）；仅3例检测DOG-1，全部阳性（3/3）。D842V突变患者根治性切除后3年无复发生存率为51.9%，非D842V突变患者为62.5%，差异无统计学意义（P = 0.380）。D842V突变患者辅助伊马替尼治疗后无复发生存率未降低，晚期患者伊马替尼一线治疗获益率为零。
PDGFRA基因突变率低，多来源于胃GIST。D842V和非D842V突变均呈现惰性生物学行为。D842V突变GIST对伊马替尼耐药，非D842V突变GIST可从伊马替尼治疗中获益。
