胃肠道间质瘤c-KIT，PDGFRA基因突变及CD117， DOG-1蛋白的表达情况
| 作者: |
1,2陈净慈,
1吴焕文,
1陆俊良,
1周炜洵,
1梁智勇
1 中国医学科学院北京协和医院病理科，北京 100730 2 清华大学医学院基础医学系，北京 100084 |
| 通讯: |
梁智勇
Email: liangzhiyong1220@yahoo.com |
| DOI: | 10.3978/j.issn.2095-6959.2018.02.006 |
| 基金: | 分子病理研究中心创新基金(2016ZX0176-1)。 |
摘要
目的：回顾性研究分析133例胃肠道间质瘤(gastrointestinal stromal tumor，GIST)患者中c-KIT及PDGFRA基因突变情况及其中94例的CD117，DOG-1蛋白表达情况。方法：用下一代测序(next generation sequencing，NGS)及免疫组织化学方法分别检测以甲醛固定石蜡包埋的标本中c-KIT，PDGFRA基因突变及CD117，DOG-1蛋白表达情况，探讨不同基因突变形式与病变原发部位的相关性，并分析基因突变与蛋白表达之间的相关性。结果：133例GIST患者中男74例，女59例，发病年龄以40岁以上为主。原发于胃的57例，小肠59例，腹腔8例，直肠5例，肠系膜2例，盆腔2例。97例(72.9%)检测到c-KIT突变，其中79例(59.4%)存在11号外显子突变，13例(9.8%)9号外显子突变，4例(3.0%)13号外显子突变，5例(3.8%)17号外显子突变，全为双突变。9号外显子插入突变主要见于小肠；11号外显子W557_K558缺失突变主要见于胃。11例(8.3%)检测到PDGFRA突变，其中8例(6.0%)为18号外显子突变，3例(2.3%)为12号外显子突变。PDGFRA突变病例均为胃原发。94例GIST患者中，89例(94.7%)CD117阳性，92例(97.9%)DOG-1阳性；双阳性表达88例(74例c-KIT突变，4例PDGFRA突变)，CD117单独阳性1例(野生型)，DOG-1单独阳性4例(1例c-KIT突变，3例PDGFRA突变)，双阴性1例(c-KIT突变)。CD117与DOG-1蛋白表达之间呈显著相关，差异有统计学意义(P<0.01)。结论：GIST中c-KIT，PDGFRA基因突变率高。c-KIT及PDGFRA基因突变形式与GIST原发部位有关。绝大多数GIST病例CD117与DOG-1双表达，CD117与DOG-1双阴性及CD117单阳性GIST病例均十分罕见，DOG-1单阳性表达病例主要见于PDGFRA突变。对于单阳性及双阴性病例的确诊，依赖于基因检测。
关键词：
胃肠道间质瘤；c-KIT；PDGFRA；CD117；DOG-1
c-KIT and PDGFRA mutations and expression of CD117 and DOG-1 in gastrointestinal stromal tumors
CorrespondingAuthor: LIANG Zhiyong Email: liangzhiyong1220@yahoo.com
DOI: 10.3978/j.issn.2095-6959.2018.02.006
Foundation: This work was supported by the Center for Molecular Pathology, Chinese Academy of Medical Sciences & Peking Union Medical College (2016ZX0176-1).
Abstract
Objective: To analyze the mutation patterns of c-KIT and PDGFRA in 133 gastrointestinal stromal tumor (GIST) cases and expression of CD117 and DOG-1 in 94 GIST cases. Methods: Next generation sequencing (NGS) and immunohistochemistry (IHC) were used to analyze gene mutations and protein expression in formalin-fixed paraffin-embedded slides and to investigate the association between gene mutation and primary locations. Results: Among 133 GIST cases, 74 were males and 59 were females with the majority over 40 years old. There were 57 cases in the stomach, 59 in the small intestine, 8 in the abdominal cavity, 5 in the rectum, 2 in the mesenterium, and 2 in the pelvic cavity. Overall, c-KIT mutations were identified in 97 cases (72.9%): 79 of them were involved with exon 11 (59.4%), 13 with exon 9 (9.8%), 4 with exon 13 (3.0%), and 5 with exon 17 (3.8%), including 5 cases (3.8%) presented with double mutations. Exon 9 insertion was mainly identified in small intestine, whereas deletion of W557_K558 of exon 11 was common in stomach. Mutation of PDGFRA was present in 11 cases (8.3%), with 8 of them in exon 18 (6.0%), 3 in exon 12 (2.3%). All PDGFRA-mutated cases were derived from stomach. We also investigated the expression of CD117 and DOG-1 in 94 cases: 89 (94.7%) were CD117(+), 92 (97.9%) were DOG-1(+). A total of 88 cases were double positive (74 harboring c-KIT mutation and 4 harboring PDGFRA mutation), 1 case was CD117 single positive (wild-type), 4 cases were DOG-1 single positive (1 c-KIT mutated and 3 PDGFRA mutated), and 1 case was double negative (c-KIT mutated). There was significant correlation between the expression of CD117 and DOG-1 (P<0.01). Conclusion: The mutation rate of c-KIT and PDGFRA in GIST were high. There were relations between mutation form and primary location of GIST. Most GIST cases showed CD117 and DOG-1 double positive pattern, whereas double negative and CD117 single positive were rare. DOG-1 single positive cases were mainly found in PDGFRA-mutated cases. Gene analysis is essential for diagnosis of GIST in single positive and double negative cases.
Keywords：
gastrointestinal stromal tumor; c-KIT; PDGFRA; CD117; DOG-1