FOXL 2基因检测对卵巢成年型粒层细胞瘤诊断与鉴别诊断的价值  

VALUE OF FOXL2 GENE DETECTION IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF OVARIAN ADULT GRANULOSA CELL TUMOR

作　　者：姜忠彩 任卫红[1,2] 王琼 窦福贤 宋欣 倪艳颖 刘爱军 JIANG Zhongcai;REN Weihong;WANG Qiong;DOU Fuxian;SONG Xin;NI Yanying;LIU Aijun(Department of Pathology,PLA General Hospital,Beijing 100853,China)

机构地区：[1]中国人民解放军总医院第一医学中心病理科,北京100853 [2]航空总医院病理科

出　　处：《精准医学杂志》2020年第1期11-14,20,共5页Journal of Precision Medicine

基　　金：国家科技部基金(2018YFC1003103);中国人民解放军总医院扶持创新基金(2016FCCXYY-2012)。

摘　　要：目的探讨FOXL 2基因突变在卵巢成年型粒层细胞瘤(AGCT)病理诊断及鉴别诊断中的意义。方法收集2012年1月—2018年12月于中国人民解放军总医院第一医学中心及航空总医院病理科同期诊断为卵巢AGCT及卵泡膜-纤维瘤患者的标本各26例,对标本进行形态学观察及免疫组织化学检测,并行Sanger测序检测FOXL 2基因突变情况。结果26例AGCT镜下瘤细胞呈弥漫型、条索状、缎带状和岛状结构排列,可见微滤泡结构(Call-Exner小体);肿瘤细胞界限不清,胞浆稀少,细胞核圆形、卵圆形,可见核沟。卵泡膜-纤维瘤镜下肿瘤细胞呈编织状、旋涡状排列;细胞以肥胖的短梭形细胞为主,核卵圆形,胞浆呈空泡状,富含脂质。免疫组织化学检测结果显示,波形蛋白(Vimentin)、抑制素a(Inhibin-a)、钙网膜蛋白(Calretinin)、CD56、CD99在AGCT中阳性表达率分别为100%、88.0%、92.8%、62.5%、40.0%;在卵泡膜-纤维瘤中阳性表达率分别为100%、76.9%、73.1%、0、0,其中两组间性索间质标记物Inhibin-a、Calretinin的表达比较无显著性差异(P>0.05)。Sanger测序检测显示,73.1%(19/26)的卵巢AGCT患者的标本中检测到FOXL 2402c.C→G突变,而卵泡膜-纤维瘤患者的标本中未检测到该突变,两者比较差异有显著意义(χ^2=8.089,P<0.05)。结论FOXL 2基因突变可用于AGCT诊断,组织学不典型病例进行基因突变和相应的免疫组化标志物检测,可以提高AGCT鉴别诊断的准确性。Objective To investigate the significance of FOXL 2 mutation in the pathological diagnosis and differential dia-gnosis of ovarian adult granulosa cell tumor(AGCT).Methods A total of 26 samples of AGCT and 26 samples of ovarian thecoma-fibroma were collected from the patients who were diagnosed with AGCT or ovarian thecoma-fibroma in The First Clinical Center of Chinese PLA General Hospital and Department of Pathology,Aviation General Hospital,from January 2012 to December 2018.Morphological observation and immunohistochemistry were performed for these samples,and Sanger sequencing was performed to detect FOXL2 gene mutation.Results The microscopic observation of 26 AGCT samples showed diffuse,strip-like,ribbon-like,and insular-like arrangement of tumor cells,with the presence of microfollicular structures(Call-Exner body),and tumor cells had unclear boundaries,sparse cytoplasm,round or oval nuclei,and visible nuclear groove.The microscopic observation of the samples of ovarian thecoma-fibroma showed interlaced and spiral arrangement of tumor cells,and the cells were mainly in the short spindle shape with oval nuclei and cytoplasm with vacuoles and rich lipids.Immunohistochemistry showed that the positive rates of Vimentin,Inhibin-a,Calretinin,CD56,and CD99 were 100%,88.0%,92.8%,62.5%,and 40.0%,respectively,in AGCT,while their positive rates were 100%,76.9%,73.1%,0,and 0,respectively,in ovarian thecoma-fibroma;there were no significant differences in the expression of the sex cord-stromal markers Inhibin-a and Calretinin between the experimental group and the control group(P>0.05).Sanger sequencing revealed a FOXL2402c.C→G mutation in 73.1%(19/26)of the samples of ovarian AGCT,while this mutation was not found in the samples of ovarian thecoma-fibroma,and there was a significant difference between them(χ^2=8.089,P<0.05).Conclusion FOXL2 mutation can be used in the diagnosis of AGCT,and the detection of mutation and immunohistochemical markers can improve the accuracy of the differential diagnosis of AGCT.

关 键 词：粒层细胞瘤 卵泡膜细胞瘤 叉头框蛋白L2 病理学 基因检测 免疫组织化学 诊断 诊断 鉴别 

分 类 号：R737.31[医药卫生—肿瘤] R446.7[医药卫生—临床医学]