卵巢低级别浆液性肿瘤中KRAS、NRAS、PIK3CA、BRAF突变及其与患者临床病理特征和激素表达的相关性分析  

Correlation analysis of KRAS,NRAS,PIK3CA,and BRAF mutations with clinicopathological features and hormone expression in ovarian low-grade serous tumors

作　　者：陆婷 张娟娟 王晚璞[2] 韦红果 魏金玲 张勇[1] 王丽 Lu Ting;Zhang Juan-Juan;Wang Wan-Pu;Wei Hong-Guo;Wei Jin-Ling;Zhang Yong;Wang Li(Department of Oncology,the First Affiliated Hospital of Kunming Medical University,Kunming,Yunnan 650500,China;Department of Pathology,the First People's Hospital of Yunnan Province,Kunming,Yunnan 650500,China)

机构地区：[1]昆明医科大学第一附属医院肿瘤科,云南昆明650500 [2]云南省第一人民医院病理科,云南昆明650500

出　　处：《解放军医学杂志》2022年第8期809-816,共8页Medical Journal of Chinese People's Liberation Army

基　　金：万人名医计划项目(KH-SWR-MY-2020-007)。

摘　　要：目的探究卵巢低级别浆液性肿瘤中KRAS、NRAS、PIK3CA、BRAF的突变状态及其与临床病理特征、激素表达水平之间的关系。方法收集2017年1月-2021年4月在云南省第一人民医院行手术治疗的低级别浆液性肿瘤(包括23例普通型浆液性交界性肿瘤、27例微乳头型浆液性交界性肿瘤和14例低级别浆液性癌)患者的组织标本进行回顾性分析。采用扩增阻碍突变系统-聚合酶链反应技术检测人类KRAS、NRAS、PIK3CA及BRAF基因的突变状态;采用免疫组化检测肿瘤组织中雌激素、孕激素受体的表达状态;分析基因突变状态与临床病理特征、激素表达水平的相关性。结果64例肿瘤组织中共检测出36例突变,其中KRAS突变21例、BRAF突变12例、PIK3CA突变2例、NRAS突变1例。KRAS、BRAF突变常见于≤35岁的年轻女性。在KRAS突变亚型中,G12S、G12D突变常见于微乳头型浆液性交界性肿瘤(P<0.05),G12C、G12R、G12V、G12A、G13C突变常见于普通型浆液性交界性肿瘤(P<0.05),G13D突变仅在低级别浆液性癌中检出。BRAF突变均见于疾病早期阶段。免疫组化结果显示,雌激素受体和孕激素受体阳性率均为76.6%(49/64),普通型浆液性交界性肿瘤与微乳头型浆液性交界性肿瘤的阳性率相似,但均明显高于低级别浆液性癌(P<0.05)。KRAS G13D突变与孕激素受体低表达明显相关(P<0.05)。结论各基因突变之间相互排斥。KRAS突变是卵巢浆液性肿瘤的致癌驱动因子,不同突变亚型与组织学类型、孕激素受体表达状态有关。BRAF突变率随着疾病进展而逐渐降低,与多种良好预后相关的临床病理特征有关,可能对疾病的进展有保护作用。PIK3CA、NRAS突变率较低。Objective To explore the mutation status of KRAS,NRAS,PIK3CA,and BRAF,and the relations with clinicopathological features and hormone expression levels in ovarian low-grade serous tumors.Methods Tissue specimens(23 cases of common-type serous borderline tumor,27 cases of micropapillary serous borderline tumor and 14 cases of low-grade serous carcinoma)were collected from the First People's Hospital of Yunnan Province during January 2017 to April 2021,and then retrospectively analyzed.The mutation status of human KRAS,NRAS,PIK3CA and BRAF genes were detected by expression status in tumor tissues was detected by immunohistochemistry,the relationship was analyzed between gene mutation status and clinicopathological features and hormone expression levels.Results A total of 36 mutations were detected in 64 tumor tissues,including 21 KRAS mutation,12 BRAF mutation,2 PIK3CA mutation and 1 NRAS mutation.KRAS and BRAF mutations were common in younger women≤35 years old.In the KRAS mutant subtype,G12S and G12D mutations are common in micropapillary serous borderline tumor(P<0.05);G12C,G12R,G12V,G12A,and G13C mutations are common in common-type serous borderline tumor(P<0.05);G13D mutation was only detected in low-grade serous carcinoma.Patients with BRAF mutations were all seen in the early stages of the disease.Immunohistochemistry showed the positive expression rates of both estrogen receptor and progesterone receptor were 76.6%(49/64).The positive expression rate of common-type serous borderline tumor was similar to that of micropapillary serous borderline tumor,and both of them were significantly higher than that in lower-grade serous carcinoma(P<0.05).KRAS G13D mutation was significantly associated with low progesterone expression(P<0.05).Conclusion Gene mutations were mutual exclusion.KRAS mutation was an oncogenic driving factor in serous tumors,and different mutant subtypes were associated with histological type and progesterone receptor expression status.As the disease progresses,BRAF mutation rate gradually dec

关 键 词：基因 KRAS 基因 NRAS 基因 PIK3CA 基因 BRAF 卵巢浆液性肿瘤 激素 突变 

分 类 号：R711.75[医药卫生—妇产科学]