在患有上皮性卵巢癌(EOC)的女性中,很少报道BRCA1和BRCA2基因中致病性变异的携带者为双突变(BRCA1/2DM)。
我们回顾了英文文献,并询问了三个报告携带BRCA1/2DM的EOC患者的资料库。将36例携带种系BRCA1/2DM的EOC患者的临床病理参数与COEUR队列中具有已知种系BRCA1/BRCA2突变携带者状态的高级别浆液性EOC女性进行了比较(n=376例非携带者,n=65BRCA1和n=38BRCA2)。评估的临床病理参数是诊断时的年龄,疾病阶段,杂合性丢失,突变类型,免疫组织化学谱,进展发生和生存。
BRCA1/2DM患者诊断年龄中位数为51.9岁,类似于BRCA1突变携带者(49.7年,p=.58),并且比BRCA2突变携带者年轻(58.1岁,p=.02)。大多数患者被诊断为晚期(III-IV;82%),并且是创始人/频繁突变的携带者(69%)。组织免疫染色显示无孕激素受体表达和低上皮内炎症。5年生存率(60%)明显低于BRCA2突变携带者(76%,p=.03),但不是BRCA1突变携带者(51%,p=.37)。
我们的数据表明两种突变都有一定的共显性效应,但这些患者的预后与BRCA1突变携带者的预后因素更为相似。
Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).
We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of
heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.
Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).
Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.