无高危家族史卵巢癌胚系基因BRCA突变及临床病理特点

Germline BRCA mutation and clinicopathological features of sporadic ovarian cancer

目的探究无高危家族史卵巢癌BRCA1/2突变与临床病理及预后的相关性。方法选取2017年6月至2019年6月青岛大学医学院附属医院收治的病理诊断为原发性卵巢癌且家族中无乳腺癌或卵巢上皮性癌病史、本人无乳腺癌病史的卵巢癌患者95例,利用二代测序技术(NGS)检测BRCA基因突变情况,并分析突变组与非突变组的临床病理资料及其与预后的关系。结果95例无高危家族史卵巢癌患者中BRCA1/2突变11例,突变率11.6%。BRCA突变组治疗前大量腹水(≥500mL)患者显著少于非突变组(P<0.05),突变组患者的化疗敏感率显著高于非突变组(P<0.05),突变组与非突变组的发病年龄、肿瘤家族史、治疗前CA125/HE4水平、肿瘤病理类型、肿瘤分期、肿瘤分化、淋巴结转移及手术满意度均无显著差异(P>0.05)。Kaplan-Meier分析结果显示,BRCA突变情况、发病年龄、初治腹水量、肿瘤分期、化疗敏感性、手术满意度对患者无进展生存期(PFS)影响有显著统计学意义(P<0.05),初治腹水量、肿瘤分期、手术满意度、化疗敏感性对患者总生存期(OS)影响具有显著统计学意义(P<0.05)。Cox回归分析结果显示,仅有化疗敏感性是无高危家族史卵巢癌患者PFS的独立影响因素,初治腹水量、手术满意度、化疗敏感性为无高危家族史卵巢癌患者OS的独立影响因素。结论BRCA基因突变在无高危家族史卵巢癌患者中仍有较高突变率,BRCA突变与临床、病理及预后存在相关性,对临床有指导意义。

Objective:To investigate the correlation between BRCA1/2 mutation and clinicopathology and prognosis of ovarian cancer without high-risk family history.Methods:A total of 95 patients admitted to the Affiliated Hospital of Qingdao University from June 2017 to June 2019 were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history.The BRCA gene mutations were detected by next-generation sequencing(NGS),the clinicopathological differences and prognosis between the mutant group and the non-mutant group were analyzed.Results:There were 11 cases of BRCA1/2 mutation in 95 cases,and the mutation rate was 11.6%.The number of patients with massive ascites(≥500mL)before treatment in BRCA mutation group was significantly lower than that in non-mutation group(P<0.05),and the chemotherapy sensitivity in mutation group was significantly higher than that in non-mutation group(P<0.05).There were no significant differences in age of onset,family tumor history,CA125/HE4 level before treatment,tumor pathological type,tumor stage,tumor differentiation,lymph node metastasis and surgical satisfaction between the mutant group and the non-mutant group(P>0.05).Kaplan-Meier analysis showed that BRCA mutation,age of onset,initial volume of ascites,tumor stage,sensitivity of chemotherapy and surgical satisfaction had significant effects on progression-free survival(PFS)of patients(P<0.05).The overall survival(OS)of patients was significantly affected by initial volume of ascites,tumor stage,surgical satisfaction and sensitivity to chemotherapy(P<0.05).Cox regression analysis showed that only sensitivity of chemotherapy was an independent influence factor of PFS in ovarian cancer patients without high-risk family history,while initial volume of ascites,surgical satisfaction,and sensitivity of chemotherapy were independent influence factors of OS in ovarian cancer patients without high-risk family history.Conclusion:BRCA gene mutation still has a high rate in ovarian cancer patients without high-risk family history.BRCA mutation is correlated with clinical and pathological information and prognosis,which has clinical guiding significance for clinical decision.