Rudaitis Vilius, Mikliusas Vismantas, Januska Gediminas, Jukna Povilas, Mickys Ugnius, Janavicius Ramunas
Vilnius University Hospital Santaros Clinics, Department of Gynecology, Santariskiu st. 2, Vilnius, Lithuania; Vilnius University, Faculty of Medicine, Clinic of Obstetrics and Gynaecology, Ciurlionio st. 21, Vilnius, Lithuania; Vilnius University Hospital Santaros Clinics, Centre of Pathology, P.Baublio st. 5, Vilnius, Lithuania.
Vilnius University Hospital Santaros Clinics, Department of Gynecology, Santariskiu st. 2, Vilnius, Lithuania; Spital STS AG, Frauenklinik, Krankenhausstrasse 12, Thun, Switzerland.
Eur J Obstet Gynecol Reprod Biol. 2020 Apr;247:26-31. doi: 10.1016/j.ejogrb.2020.01.040. Epub 2020 Jan 30.
Due to ineffective ovarian cancer (OC) screening programs, prophylactic bilateral salpingo-oophorectomy (PBSO) is suggested for BRCA1/2 genes mutation carriers. The reported incidence of clinically occult neoplasia and OC detected during PBSO varies widely (2-17 %), reflecting differences in studies design.
We aimed to prospectively evaluate the incidence of occult neoplasia in specimens collected during PBSO performed in a single tertiary center and to determine the effectiveness of this procedure in BRCA1/2 mutation carriers.
Between January 2010 and October 2016 a total of 564 new germline BRCA1/2 mutation positive women were identified and 71 carriers underwent laparoscopic PBSO. Patients were prospectively followed-up after the surgery and data on operation, age, complications, histological reports and BRCA1/2 gene mutation types were collected and analyzed.
Serous tubal intraepithelial carcinoma (STIC) was diagnosed in 7 (9.85 %) and OC in 4 (5.6 %) women (one advanced (FIGO IIIC) and 3 early (FIGO IA/C) stages); total incidence 15.5 %. Women's mean age at the time of surgery was 46.5 years. The mean age of women diagnosed with STIC and OC was 45.9 years (42-64). The mean follow up time for women being diagnosed with OC/STIC was 3.72 years; no recurrence was observed. The median time to perform laparoscopic PBSO was 43 min. (ranging from 25 to 65 min.), no surgical complications occurred during this operation. Interestingly, we found statistically significant (P = 0.0105) enrichment of STIC lesions in BRCA1 c.4035delA (an established Baltic founder mutation) carriers group.
The incidence of pathological findings in BRCA1/2 mutation carries after PBSO is sufficiently high and our prospective study data supports PBSO as the most effective measure for reducing the risk of OC in BRCA1/2 mutation carriers. A novel finding of the enrichment of STIC lesions in BRCA1 c.4035delA carriers may show important biological differences in OC tumorigenesis between different BRCA1 mutations, which warrant further investigations.
由于卵巢癌（OC）筛查项目效果不佳，建议对BRCA1/2基因突变携带者进行双侧预防性输卵管卵巢切除术（PBSO）。据报道，PBSO期间检测到的临床隐匿性肿瘤和OC的发生率差异很大（2%-17%），这反映了研究设计的差异。
我们旨在前瞻性评估在单一三级中心进行PBSO时所采集标本中隐匿性肿瘤的发生率，并确定该手术对BRCA1/2突变携带者的有效性。
2010年1月至2016年10月期间，共确定了564名新的种系BRCA1/2突变阳性女性，71名携带者接受了腹腔镜PBSO。术后对患者进行前瞻性随访，收集并分析手术、年龄、并发症、组织学报告和BRCA1/2基因突变类型的数据。
7名（9.85%）女性被诊断为浆液性输卵管上皮内癌（STIC），4名（5.6%）女性被诊断为OC（1例晚期（国际妇产科联盟（FIGO）IIIC期）和3例早期（FIGO IA/C期））；总发生率为15.5%。手术时女性的平均年龄为46.5岁。被诊断为STIC和OC的女性的平均年龄为45.9岁（42-64岁）。被诊断为OC/STIC的女性的平均随访时间为3.72年；未观察到复发。进行腹腔镜PBSO的中位时间为43分钟（范围为25至65分钟），手术期间未发生手术并发症。有趣的是，我们发现BRCA1 c.4035delA（一种已确定的波罗的海始祖突变）携带者组中STIC病变有统计学意义的富集（P = 0.0105）。
PBSO后BRCA1/2突变携带者的病理发现发生率足够高，我们的前瞻性研究数据支持PBSO作为降低BRCA1/2突变携带者OC风险的最有效措施。BRCA1 c.4035delA携带者中STIC病变富集这一新发现可能表明不同BRCA1突变在OC肿瘤发生过程中的重要生物学差异，值得进一步研究。
