BRCA1 和 BRCA2 双重杂合性上皮性卵巢癌女性的临床病理特征：系统评价和病例报告分析。

Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis.

机构信息

Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada.

Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada; Department of Pathology, Centre hospitalier de l'Université de Montreal (CHUM), Montreal, QC, Canada.

出版信息

Gynecol Oncol. 2020 Feb;156(2):377-386. doi: 10.1016/j.ygyno.2019.11.019. Epub 2019 Nov 18.

DOI:10.1016/j.ygyno.2019.11.019

PMID:31753525

Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

BRCA1 和 BRCA2 基因致病变异携带者（双突变，BRCA1/2 DM）在患有上皮性卵巢癌（EOC）的女性中很少见。

方法

我们查阅了英文文献，并对三个报告携带 BRCA1/2 DM 的 EOC 患者的数据库进行了查询。将 36 例携带种系 BRCA1/2 DM 的 EOC 患者的临床病理参数与 COEUR 队列中已知种系 BRCA1/BRCA2 突变携带者状态的高级别浆液性 EOC 女性（无携带者 376 例，BRCA1 携带者 65 例，BRCA2 携带者 38 例）进行比较。评估的临床病理参数包括诊断时的年龄、疾病分期、杂合性丢失、突变类型、免疫组织化学特征、进展发生和生存。

结果

BRCA1/2 DM 患者的中位诊断年龄为 51.9 岁，与 BRCA1 突变携带者（49.7 岁，p=0.58）相似，且比 BRCA2 突变携带者年轻（58.1 岁，p=0.02）。大多数患者诊断为晚期（III-IV 期；82%），并携带常见/频发突变（69%）。组织免疫染色显示孕激素受体表达缺失和上皮内炎症程度低。5 年生存率（60%）明显低于 BRCA2 突变携带者（76%，p=0.03），但与 BRCA1 突变携带者（51%，p=0.37）无差异。